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The presence of cross-reacting antigens between Paragonimus westermani, Schistosoma mansoni, and Fasciola hepatica adult worms was demonstrated by Ouchterlony immunodiffusion and enzyme-linked immunosorbent assay (ELISA). A serum bank was developed against the three trematode genera to serve as probes to determine the presence of cross-reacting antibodies to P. westermani worm extracts. In this manner, it was possible to demonstrate that antigens common to F. hepatica and S. mansoni tegument were also present in P. westermani worm extracts. Likewise, it was possible to demonstrate that the F. hepatica antigens which bind to Concanavalin A, as well as the subfraction which in isoelectric focusing has a pI of 4.2, were also found in P. westermani worms. Also, a monospecific polyclonal serum to a Fasciola/Schistosoma cross-reacting antigen and the anti-P. westermani serum both reacted in Ouchterlony immunodiffusion with the P. westermani antigenic extract, each producing a line which linked with each other indicating common antigenic determinants and suggesting a common antigen among the digenetic trematodes. Finally, the P. westermani antigenic extracts induced in mice the production of antibodies which reacted with S. mansoni adult worm antigens by ELISA. As all of the Fasciola and Schistosoma sera were prepared against antigenic preparations which induced in mice protection to challenge infection with S. mansoni, this suggested that the P. westermani worms also contain protective antigens against S. mansoni. Immunity to Schistosoma mansoni infection was induced in mice by vaccination with Paragonimus westermani whole worm extracts (PwWWE). Immunized mice showed as high as a 67% worm burden reduction over controls. High doses of PwWWE did not confer protection to S. mansoni infection. Thus, in this study, immunity in heterologous systems was demonstrated and the existence of a common protective antigen shared by the digenetic trematodes was suggested.