To determine whether chronic Schistosoma mansoni infection interferes with hepatitis B virus (HBV) immunization, 308 schoolchildren aged 6-12 years with no evidence of prior HBV infection (156 with active schistosomiasis) were vaccinated with three 5-micrograms injections of recombinant DNA-derived HBV vaccine. The vaccine was given in the deltoid muscle at time 0 and 1 and 7 months later. All vaccinees were examined 1 and 3 years after vaccination for quantitative antibody to hepatitis B surface antigen (anti-HBs). Seroconversion was detected in 284 vaccinated children (92%), of whom 271 had a good (51-300 mIU/mL) or excellent (greater than 300 mIU/mL) anti-HBs response. Sixteen other children (5%) had evidence of natural HBV infection (antibody to hepatitis B core antigen). Of those with good or excellent response, 99% retained high antibody titers for 3 years. Response was not influenced by S. mansoni infection. Hepatomegaly and splenomegaly were associated with reduced vaccine response.