This article explores the ways in which French colonial authorities met the life and death challenge represented by the re-emergence of yellow fever epidemics in Saint-Louis-du-Sénégal at a time when physicians knew very little about the etiology, diagnosis, transmission and treatment of most infectious and parasitic diseases. The discussion focuses on changing strategies and policies designed to address yellow fever threats, the attitudes and priorities of the authorities, the limits of ‘colonial medicine’ and the responses of people affected by sanitary measures. The article argues that because of the ignorance of the etiology and epidemiology of yellow fever, policies were misdirected and did not achieve their primary goals. Even after the introduction of germ theory, the gap between medical thinking and practice persisted for another decade. The African urban working class and underclass were the first victims of this state of affairs. The article also examines the conflict between the interests of public health, commerce and privacy rights.