Residents of institutions for the mentally handicapped, especially Down's syndrome (DS) patients, are at increased risk for exposure to hepatitis B virus (HBV). Indeed, during a serological survey of 770 mentally retarded residents in institutions in Antwerp in 1985, 32.6% of the 92 DS patients screened were HBsAg positive, compared with 7.2% of the 678 other mentally retarded (OMR) patients (p less than 0.001). Seronegative mentally handicapped individuals (275 in number including 18 DS patients) from three institutions were vaccinated with 20 micrograms of a recombinant yeast-derived hepatitis B vaccine (YDV) according to a 0, 1, 6 month schedule. Serum samples were tested at months 1, 2, 7, 12 and 24 for HBV markers by radioimmunoassay. One month after the third vaccine dose, 81.3 and 97.7% of DS and OMR patients had seroconverted, respectively, with GMTs of 516.3 and 1078.7 mIU ml-1. Two years after the start of the vaccination course, 66.7 and 96% of subjects in the two groups still had protective antibody levels (greater than or equal to 10 mIU ml-1), although GMTs had decreased to 40.1 and 166.3 mIU ml-1 in the two groups, respectively. Only one of the 18 DS patients had transient asymptomatic anti-HBc infection at month 2, no subject followed up being infected after the full vaccination course. Thus, the institutionally mentally handicapped, including DS patients are capable of responding adequately to YDV.