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Because dual infection with Schistosoma mansoni and hepatitis B may lead to severe liver disease, populations living in schistosomiasis-endemic areas might benefit if effectively immunized against hepatitis B. To determine whether a plasma-derived hepatitis B vaccine is immunogenic in patients with schistosomiasis, 32 individuals infected with S. mansoni were given three 20-µg doses of Heptavax-B vaccine and treated with praziquantel. Antibody to hepatitis B surface antigen developed in 90.6% of the study subjects after three doses of vaccine. Five patients (15.6%) had a weak response to the vaccine, and three patients (9.4%) failed to develop antibody. A weak or failed response to the vaccine was significantly associated with the presence of hepatosplenomegaly. A plasma-derived vaccine is immunogenic for persons infected with S. mansoni; however, vaccine response is diminished in hepatosplenic schistosomiasis.