Mentally handicapped clients in institutions are at high risk for hepatitis B virus (HBV) infection. In 1985, 770 mentally handicapped residents from four institutions in the Antwerp area were screened for HBV markers. The prevalence of hepatitis B surface antigen was 10.3 percent (range, 6.1 to 15.2 percent); 42.3 percent (range, 11.5 to 60.1 percent) had antibodies to hepatitis B surface antigen and the hepatitis B core antigen. In 1986, 275 seronegative mentally handicapped residents were vaccinated intramuscularly in the deltoid region with 20 micrograms (1.0 ml) of a recombinant deoxyribonucleic acid yeast-derived hepatitis B vaccine (Engerix-B, SmithKline Biologicals, Rixensart, Belgium) on a zero-, one-, six-month schedule. Serum samples were collected at Months 1, 2, 7, 12, and 24 and were tested for HBV markers by radioimmunoassay. The seroconversion rates for hepatitis B surface antigen antibodies were 39 percent at Month 1 (geometric mean concentration, 6.4 IU/liter), 82 percent at Month 2 (geometric mean concentration, 23.4 IU/liter), 97 percent at Month 7 (geometric mean concentration, 1,034 IU/liter), and 96 percent at Month 12 (geometric mean concentration, 269 IU/liter). Among the 214 residents evaluated at Month 12, 69 percent had hepatitis B surface antigen antibody levels greater than 100 IU/liter (geometric mean concentration, 603 IU/liter). No significant adverse reactions were observed. Within the first seven months of observation, HBV infection was detected in eight of 271 subjects (estimated annual incidence of 5 percent). During this period, none of the clients developed clinical hepatitis or showed biochemical evidence of liver damage. Between eight and 24 months, no additional HBV infections were detected. These data can be compared with an annual incidence of HBV infection of 8.7 percent in a historical cohort of mentally handicapped residents in one of the four institutions.