Immunity to infection due to Schistosoma mansoni was induced in CBA/J mice by using a tegument antigen from Fasciola hepatica worms. Multiple immunizations resulted in up to 83% higher worm-burden reductions than did single immunizations. The vaccine also had an adverse effect on the fecundity of female schistosome worms, which resulted in a lower number of eggs per worm pair recovered from the livers of infected mice. Mice immunized once with tegument antigens of F. hepatica survived lethal doses of S. mansoni cercariae for longer periods than did control mice. These results--lowered worm-burden recoveries, lower egg burdens per worm pairs resulting in lesser numbers of granulomatous lesions, and longer survival times--in immunized mice suggest that protection against infection due to S. mansoni is possible using soluble antigens as vaccines.