The power of the MacCullochs on the national stage entered into decline after the reign of James IV. However, the family remained significant within Galloway, and a number of influential landholding branches sprung off the main Myreton line. The McCulloch lairds of Ardwell and Killasser were among the leading Galloway supporters of Mary, Queen of Scots, summoned with the threat of a charge of treason to submit to the regency ruling after her deposition in 1569 and 1571. David, son of Thomas McCulloch of Nether Ardwall was in military service in the Thirty Years War, and settled permanently on the continent; his sons Thomas and Anthony were officers in a British regiment in Spanish service during the War of Devolution (1667-8) against Louis XIV. A second David McCulloch of Nether Ardwall served in the armies of William of Orange before the 1688 Revolution, and then in the British forces in the Nine Years' War (1688–97). In 1715, he was offered but declined a commission in the Jacobite rebel army, commanded by his cousin the sixth Viscount Kenmure. In the earlier part of the seventeenth-century, the brothers John and James McCulloch, younger sons of the McCullochs of Killasser, attained distinction as scholars and physicians, both holding professorial chairs at the University of Pisa, and both serving as physicians-in-ordinary to King James VI/I. John McCulloch had worked previously as physician to the Holy Roman Emperor Rudolf II, who shared his enthusiasm for alchemy and astrology.