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Major epidemics of plague in Germany and France in the early eighteenth century and in Moscow in the 1770s brought an end to a series of epidemic disasters in Europe which had started with the Black Death. The article examines what they had in common, and seeks to understand why they should have ended when they did. It shows that European governors were unanimous in insisting on rigid quarantine and other measures for containing the disease developed over previous centuries, despite their ignorance of plague’s precise causes. It shows also that physicians across Europe were more deeply divided than they had ever been on the issue of contagion, and now engaged in an international dispute about whether the acknowledged cruelties inflicted by compulsory quarantines were wholly counterproductive, or a price worth paying for the prevention of still worse disasters. The article concludes by drawing on recent work on plague in the Ottoman Empire, and on research into the ancient DNA of the second pandemic, in order to set the epidemic history of western Europe in a wider comparative context.