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Rh made this action a casus belli. The Genoese won a victory in the gulf of Alexandretta (1294); but on the other hand the Venetians under Ruggiero Morosini forced the Dardanelles and sacked the Genoese quarter of Galata. The decisive engagement, however, of this campaign was fought at Curzola (1299) in the Adriatic, when Venice suffered a crushing defeat. A peace, honourable to both parties, was brought about by Matteo Visconti, lord of Milan, in that same year. But the quarrel between the republics, both fighting for trade supremacy—that is to say, for their lives—could not come to an end till one or other was thoroughly crushed. The fur trade of the Black Sea furnished the pretext for the next war (1355–54), which ended in the crushing defeat of Venice at Sapienza, and the loss of her entire fleet. But though Venice herself seemed to lie open to the Genoese, they took no advantage of their victory; they were probably too exhausted. The lord of Milan again arranged a peace (1355).

We have now reached the last phase of the struggle for maritime supremacy. Under pressure from Venice the emperor John V. Palaeologus granted possession of the island of Tenedos to the republic. The island commanded the entrance to the Dardanelles. Genoa determined to oppose the concession, and war broke out. The Genoese Admiral Luciano Doria sailed into the Adriatic, attacked and defeated Vettor Pisani at Pola in Istria, and again Venice and the lagoons lay at the mercy of the enemy. Doria resolved to blockade and starve Venice to surrender. He was master of the sea, and the flow of provisions from the mainland was cut off by Genoa's ally, Francesco I. Carrara, lord of Padua. Doria seized Chioggia as a base of operations and drew his fleet inside the lagoons. The situation was extremely critical for Venice, but she rose to the occasion. Vettor Pisani was placed in command, and by a stroke of naval genius he grasped the weakness of Doria's position. Sailing to Chioggia he blocked the channel leading from the lagoon to the sea, and Doria was caught in a trap. Pisani stationed himself outside the Lido, on the open sea, to intercept relief should any appear, and Doria, instead of blockading Venice, was himself blockaded in Chioggia. For many months the siege went on; but Pisani gradually assumed the offensive as Genoese spirits and food ran low. Finally, in June 1380 the flower of the Genoese fleet surrendered at discretion. Genoa never recovered from the blow, and Venice remained undisputed mistress of the Mediterranean and the Levant trade.

The defeat of Genoa and the establishment of Venetian supremacy in the Mediterranean brought the state to a further step in its development. The undisputed mastery of the eastern trade increased its bulk in Venice. But as the city became the recognized mart for exchange of goods between east and west, the freedom of the western outlet assumed the aspect of a paramount question. It was useless for Venice to accumulate eastern merchandise if she could not freely pass it on to the west. If the various states on the immediate mainland could levy taxes on Venetian goods in transit, the Venetian merchant would inevitably suffer in profits. The geographical position of Venice and her commercial policy alike compelled her to attempt to secure the command of the rivers and roads of the mainland, at least up to the mountains, that is to say, of the north-western outlet, just as she had obtained command of the south-eastern inlet. She was compelled to turn her attention, though reluctantly, to the mainland of Italy. Another consideration drove her in the same direction. During the long wars with Genoa, after the defeats of Curzola, Sapienza, Pola, above all during the crisis of the war of Chioggia, it had been brought home to the Venetians that, as they owned no meat or corn-producing territory, a crushing defeat at sea and a blockade on the mainland exposed them to the grave danger of being starved into surrender. Both these pressing necessities, for a free outlet for merchandise and for a food-supplying area, drove Venice on to the mainland, and compelled her to initiate a policy which eventually landed her in the disastrous wars of Cambrai. The period with which we are now dealing is the epoch of the despots, the signori, and in pursuit of expansion on the mainland Venice was brought into collision first with the Scaligeri of Verona, then with the Carraresi of Padua, and finally with the Visconti of Milan. Hitherto Venice had enjoyed the advantages of isolation; the lagoons were virtually impregnable; she had no land frontier to defend. But when she touched the mainland she at once became possessed of a frontier which could be attacked, and found herself compelled either to expand in self-defence or to lose the territory she had acquired.

Venice had already established a tentative hold on the immediate mainland as early as 1339. She was forced into war by Mastino della Scala, lord of Padua, Vicenza, Treviso, Feltre and Belluno, as well as of Verona, who imposed a duty on the transport of Venetian goods. A league against the Scala domination was formed, and the result was the fall of the family. Venice took possession of Padua, but in the terms of the league she at once conferred the lordship on the Carraresi, retaining Treviso and Bassano for herself. But it is not till we come to the opening of the next century that Venice definitely acquired land possessions and found herself committed to all the difficulties and intricacies of Italian mainland politics. On the death of Gian Galeazzo Visconti in 1402, his large possessions broke up, His neighbours and his generals seized what was nearest to hand. Francesco II. Carrara, lord of Padua, attempted to seize Vicenza and Verona. But Venice had been made to suffer at the hands of Carrara, who had levied heavy dues on transit, and moreover during the Chioggian War had helped the Genoese and cut off the food supply from the mainland. She was therefore forced in self-defence to crush the family of Carrara and to make herself permanently mistress of the immediate mainland. Accordingly when Gian Galeazzo's widow applied to the republic for help against Carrara it was readily granted, and, after some years of fighting, the possessions of the Carraresi, Padua, Treviso, Bassano, commanding the Val Sugana route, as well as Vicenza and Verona, passed definitely under Venetian rule. This expansion of mainland territory was followed in 1420 by the acquisition of Friuli after a successful war with the emperor Sigismund, thus bringing the possessions of the republic up to the Carnic and Julian Alps, their natural frontier on the north-east.

Venice was soon made to feel the consequences of having become a mainland power, the difficulties entailed by holding possessions which others coveted, and the weakness of a land frontier. To the west the new duke of Milan, Filippo Maria Visconti, was steadily piecing together the fragments of his father's shattered duchy. He was determined to recover Verona and Vicenza from Venice, and intended, as his father had done, to make himself master of all north Italy. The conflict between Venice and Milan led to three wars in 1426, 1427 and 1429. Venice was successful on the whole. She established her hold permanently on Verona and Vicenza, and acquired besides both Brescia and Bergamo; and later she occupied Crema. The war of Ferrara and the peace of Bagnolo (1484) gave her Rovigo and the Polesine. This, with the exception of a brief tenure of Cremona (1499–1512), formed her permanent territory down to the fall of the republic. Her frontiers now ran from the seacoast near Monfalcone, following the line of the Carnic and Julian and Raetian Alps to the Adda, down the course of that river till it joins the Po, and thence along the line of the Po back to the sea. But long and exhausting wars were entailed upon her for the maintenance of her hold. The rapid formation of this land empire, and the obvious intention to expand, called the attention not only of Italy but of Europe to this power which seemed destined to become supreme in north Italy, and eventually led to the league of Cambrai for the dismemberment of Venice. Contemporaneously other events were menacing the ascendancy and exhausting the treasury of the republic. In 1453 Constantinople fell to the Ottoman Turks, and although Venice entered at once into treaty with the new power and desired to trade with it, not to fight with it, yet it was impossible that her possessions