Protective immunity to Toxoplasma was studied in hamsters. Immunity developed in 2 to 3 weeks after vaccinations were performed. Vaccination with live RH, T-45, and ts-4 strains afforded the best protection against challenge exposure with the most pathogenic RH strain used. Even a killed-toxoplasma vaccine protected all hamsters against the slightly less pathogenic T-1 strain through 24 weeks, but it did not protect hamsters against challenge exposure with the RH strain. Both ts-4, a nonpersistent strain, and killed-toxoplasma vaccine provided protective immunity in hamsters that was not dependent upon premunition. Toxoplasma antibody titers in hamsters given the 2 vaccines were similar. However, there was a difference in the quality of immunity: fever and body weight loss were seen in hamsters vaccinated with the killed-toxoplasma vaccine after they were challenge exposed with T-1 strain, whereas these changes were rarely seen in hamsters given the live-toxoplasma vaccine and then challenge exposed with RH strain. Delayed-type hypersensitivity to Toxoplasma antigen always appeared before protective immunity and was detected in all hamsters by 4 days after vaccination with live-toxoplasma strains. Although the development of delayed-type hypersensitivity preceded protective immunity, it was not indicative that protective immunity was present or would develop.