Rickettsia rickettsii causes Rocky Mountain spotted fever (RMSF), a significant public health threat with the highest fatality rate of any tick-borne disease in the United States. Our studies are aimed at evaluating the principal factors which either limit or enhance the transmission of R. rickettsii by wood ticks (Dermacentor andersoni). A better understanding of these factors will offer insight into the mechanisms infectious tick-borne bacteria employ to naturally maintain themselves in focal zones and ultimately emerge as human pathogens. The work involved in this project includes: 1) identification of endogenous tick-borne bacteria and evaluating their potential to interfere with the transmission of R. rickettsii, 2) quantification of the lethal effect of R. rickettsii on its tick vector, and 3) elucidation of the mechanism by which R. rickettsii transforms from the overwintering form into a virulent or reactivated stage during tick blood-feeding.