This chapter presents an ethnographic account of Kyasanur forest disease (KFD), which was first identified in March 1957 in the forest areas adjoining Shimoga District, Karnataka State, India. It considers the way in which this unfamiliar, debilitating disease was perceived and treated by South Kanarese villagers in Karnataka during the epidemic. It focuses on the social and historical conditions that provide the basis for the explanatory models of KFD, which South Kanarese villagers fashioned out of the wide range of explanations for misfortune available to them as cultural resources. It highlights the way in which certain aspects of the disease were incorporated into the social construction of its etiology. The analysis shows that Indian villagers accept multiple frames of reference for explaining the causes of a single misfortune. The question it considers is why villagers adopted one idea of causality rather than another in treating the disease.