We explore the impact of one of the earlier epidemics to hit natives living in the Hudson Bay drainage basin: the smallpox outbreak of 1780-82. We review contemporary descriptions of the epidemic and how Europeans at the time viewed its impact on the native population of the region. We then explore the impact of the epidemic using three approaches. First, we summarize the experience with other smallpox outbreaks including those among so-called 'virgin soil' populations. Next we place the epidemic in the context of the fur trade of the region; and finally, we suggest a measure of the population decline based on backward projections of later population estimates and the likely pre-epidemic population given the carrying capacity of the region in terms of large game. Our results for this particular epidemic, as we argue in the concluding section, may have broad implications for the interpretation of pre-contact aboriginal populations and the impact of European-carried disease.