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 1649 his regiment was placed on the establishment, and ordered to be completed (Commons' Journals, vi. 145, 147). It was intended to employ it in the relief of Ireland. Part of the regiment joined in the mutiny of the levellers in May 1649, but Reynolds, with those who remained faithful, dispersed some of the mutineers at Banbury, held Newbridge against them, and joined in the final suppression of the revolt at Burford (Cromwelliana, p. 57; The Moderate, 8–15 May, 15–22 May 1649). The levellers denounced him in their pamphlets as an apostate and a traitor (The Levellers Vindicated, 1649, p. 4).

Reynolds and his regiment landed at Dublin on 25 July 1649, and played an important part in the victory which Colonel Michael Jones [q. v.] gained over Ormonde at Rathmines on 2 Aug. (, Memorials of the Civil War, ii. 160;, iii. 80, 85). He captured Carrick (November 1650), and with a very small garrison successfully repulsed Lord Inchiquin's attempt to retake it [see ]. ‘Both in the taking and defending of this place,’ wrote Cromwell to the speaker, ‘Colonel Reynolds his carriage was such as deserves much honour’ (, Letter cxvi.). About April 1651 Reynolds was made commissary-general of the horse in Ireland, and in that capacity assisted in the sieges of Limerick and Galway, and signed capitulations with Colonel Fitzpatrick, Lord Clanricarde, and other Irish leaders (, Memoirs, ed. 1894, i. 262, 269, 289;, Contemporary History of Affairs in Ireland, iii. 232, 293, 304, 331). In 1653 the islands of Arran (15 Jan.) and Innisboffin (14 Feb.) surrendered to him (ib. p. 363). Parliament voted him as a reward Irish lands to the value of 500l. per annum, in pursuance of which vote the manor of Carrick was made over to him (Commons' Journals, vii. 105, 725). With the debentures he received for his pay he invested in seven thousand acres of land in the county of Cork, and also purchased other lands in Waterford (Thurloe Papers, vi. 761). In the parliament of 1654 he represented the counties of Galway and Mayo, and in that of 1656 Waterford and Tipperary.

Reynolds was a zealous supporter of Cromwell, was knighted by the Protector on 11 June 1655 (Mercurius Politicus, 7–14 June 1655), and voted for the offer of the crown to Oliver (Lansdowne MS. 823, f. 90; Harleian Miscellany, iii. 455, 464). As he married Sarah, daughter of Sir Francis Russell of Chippenham, he was the brother-in-law of Henry Cromwell, who had married her sister Elizabeth. About twenty letters from Reynolds to Henry Cromwell are among the correspondence of the latter (Lansdowne MS. 823). In March 1655 Reynolds was employed in the suppression of the intended rising of the royalists in Shropshire (, iii. 265, 298, 354). In July following he returned to Ireland with Henry Cromwell. In September 1655 the Protector thought of sending Reynolds to command in Jamaica. Henry Cromwell reported that he was willing to accept the post, but added: ‘If you take him from hence you deprive me of my right hand’ (ib. iv. 54). In November 1655 Reynolds promoted the petition for the appointment of Henry Cromwell as lord deputy, or for the return of Fleetwood to his duties in Ireland (ib. iv. 197, 421). In January 1656 Reynolds was sent to England by Henry Cromwell to give the Protector an account of the state of affairs in Ireland (ib. iv. 404). He was also charged with commissions of importance relative to the reorganisation of the Irish government (Lansdowne MS. 823, ff. 66–88). On 25 April 1657 the Protector appointed Reynolds commander-in-chief of the forces intended to co-operate with the French army in Flanders (, vi. 223, 230). His pay as commander-in-chief was five pounds per diem (ib. vi. 346). Reynolds, after some hesitation, accepted (Lansdowne MS. 823, ff. 104–108). He landed in France in May, and was received with studied courtesy by Mazarin (, vi. 297). But he found it difficult to persuade Turenne to attack the coast towns of Flanders, and complained that English interests were throughout postponed to French (ib. vi. 480). At the siege of St. Venant the English troops ‘behaved themselves very stoutly, and were one great cause of the governor's not daring to abide the utmost;’ but the six thousand men under the command of Reynolds were reduced to four thousand by September 1657, solely by the hardships of the campaign. ‘Howsoever,’ he protested, ‘if I must still fight on untill my dagger, which was a sword, become an oyster-knife, I am content and submit’ (Lansdowne MS. 823, f. 114). Mardyke was taken on 23 Sept., and Reynolds installed there as governor of the English garrison; but the task of keeping so weakly fortified a post was one of great difficulty. Though Reynolds repulsed one attack with considerable loss to the assailants (22 Oct.), both the English troops serving with Turenne and the garrison of Mardyke were so reduced by disease that at the beginning of December only eighteen hundred out of the six thousand were fit for service (ib. 823, f.