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This essay considers native and non-native evidence for smallpox around the Strait of Georgia and Puget Sound in the late eighteenth century. It concludes that smallpox devastated the Salish peoples of these regions, probably in the winter of 1781-82, reaching them via the lower Columbia from the plains where, in 1780-81, the disease was rampant. The implications of this conclusion and the reluctance of scholars to identify smallpox on the early Northwest Coast are also investigated.