Although the white-footed mouse, Peromyscus leucopus Rafinesque, has been incriminated as the main reservoir of the agent of human babesiosis, Babesia microti Franca, a quantitative demonstration of reservoir competence has not been presented. Mice captured within an intensely zoonotic site served as host for laboratory-reared larval Ixodes dammini Spielman, Clifford, Piesman, and Corwin, and the resulting nymphal ticks were assayed for evidence of salivary gland infection by the piroplasm. Solely 25% of the mice were patently parasitemic on thin blood smears, but virtually all mice infected ticks with B. microti. Thus, smear positivity correlates poorly with infectivity. Infection in smear-negative mice, however, was demonstrated by the use of the polymerase chain reaction. White-footed mice may be chronically infected by the piroplasm with parasitemias detectable only by the most sensitive methods, yet efficiently serve as a source of infection. We conclude that P. leucopus serves to maintain B. microti in the northeastern United States, as it does the spirochetal agent of Lyme disease.