Parameters of immunization of mice with 60Cobalt-irradiated Schistosoma mansoni cercariae are described and related to protection against subsequent challenge infection. Such immunization was found to be dependent on dose of irradiation, number of immunizing cercariae, and number and time course of infections. Low levels of resistance were obtained with low irradiation doses, in contrast to previous studies in mice. In general, resistance increased with increasing irradiation doses, up to approximately 48-56 Kr. Maximal resistance (70-80%) was induced by a single exposure to 250-500 cercariae, irradiated at a dose rate of 2 Kr/minute to a total dose of 56 Kr, administered percutaneously 4-6 wk prior to challenge. Challenge could be delayed for at least 15 wk after immunization without a decrease in resistance. The resistance obtained was not attributable to a delayed migration of challenge worms.