A 12 Kd antigen was isolated from Fasciola hepatica adult worm extracts by gel filtration in Sephadex G-50 and ion exchange chromatography using DEAE Sephadex A-120. Mice immunized with this Fasciola-derived 12 Kd antigen developed antibodies to Schistosoma mansoni adult worm extracts, demonstrating its cross-reactivity with schistosomes. Vaccination of mice with microgram amounts of the antigen in Freund's adjuvant induced up to 77% reduction in worm burdens after challenge with S. mansoni cercariae. F. hepatica 12 Kd degraded by proteinase K to lower molecular weight polypeptides which still retain their antigenicity as determined by the enzyme-linked immunoelectrotransfer blot technique. Treatment with either Endoglycosidase H, neuraminidase, or dithiothreitol had no effect on its mobility in sodium dodecyl sulfate polyacrylamide gels, or in its recognition by antibody, suggesting the absence of carbohydrate moieties or disulphide bonds in relation to its antigenic determinants and also suggesting that the antigen is a pure polypeptide. These studies establish that a molecularly defined cross-reactive component of one parasitic trematode (F. hepatica) induces resistance to challenge infection with another parasitic trematode (S. mansoni). Its polypeptide nature makes recombinant DNA technology an alternative for the manufacture of a vaccine.