Experiments were performed in mice on resistance to challenge with Schistosoma mansoni and S. mattheei cercariae following previous bisexual, single sex or irradiated infections. Resistance to reinfection was demonstrated following bisexual infection with S. mansoni using out-bred T.O. mice and it appeared that such resistance was not stimulated by cercarial transformation products. T. O. mice from three different suppliers exhibited markedly different levels of resistance and mortality. Bisexual infection with S. mattheei resulted in resistance to both homologous challenge and heterologous challenge with S. mansoni. Infections with S.mansoni worms of one sex only, stimulated significantly lower resistance than light bisexual infections. Injection of eggs alone failed to stimulate resistance, suggesting that both worms and eggs may be required. Studies on irradiation of S. mansoni and S. mattheei showed that the minimum radiation doses required to produce sterile infections were 2.3 kr and 2.7 kr respectively, due predominantly to sterilization of the female worms. Radiation-induced death of 2.3 kr-irradiated para sites occurred mainly in the liver. but higher doses resulted in death earlier in the migration pathway. with parasites exposed to 40 kr dying at the site of infection. Varying levels of resistance followed percutaneous or intramuscular infection with larvae irradiated with 2.3-160 kr. This resistance was demonstrated by significantly reduced worm and egg burdens and by longer survival of the vaccinated mice. Maximal resistance was demonstrated earlier following vaccination with highly irradiated parasites (20-40 kr) than with 2.3 kr-irradiated parasites, although comparable levels were eventually reached. The resistance was not transient, being demonstrated 17 weeks post-infection. Neither unirradiated male parasites alone nor dead irradiated parasites could confer resistance suggesting that, in the absence of eggs, death of the parasites within the host is necessary for the induction of resistance. Resistance was not increased by varying the number of irradiated larvae, the number of vaccinations, the route of vaccination or by the simultaneous administration of B.C.G. Irradiated S. mattheei infections conferred only weak resistance to homologous challenge and vaccination with irradiated S.mansoni or S. mattheei failed to confer significant resistance to heterologous challenge.