Previous studies on heterologous immunity in mice and rhesus monkeys have shown that immunization with Schistosoma bovis, S. mattheei or S. rodhaini cercariae can limit the severity of infection resulting from subsequent challenge with S. mansoni. The present report describes further evidence of the protection afforded by heterologous immunization. It has been demonstrated that mice immunized with S. mattheei can withstand S. mansoni infections that are lethal to normal mice and that the degree of immunity developed is influenced by the level of maturation and the duration of the initial infection, the size and number of immunizing doses, the route of exposure and the sex of the parasite.