Formalin-killed, purified Rickettsia rickettsii vaccine was evaluated in a guinea pig model of R. rickettsii infection. Vaccinated guinea pigs were partially protected by the vaccine when challenged with virulent, viable rickettsiae. Greater protection was observed when higher doses of vaccine were given and when frequent booster injections were administered. Stimulation of cell-mediated immunity to the vaccine antigens was variable and also appeared to be achieved more reproducibly with booster vaccinations. Serum antibody was elicited by high doses of vaccine and by booster vaccinations. The presence of serum antibody was useful in predicting immunity to challenge with R. rickettsii.