The immune response after vaccination with H-B-VAX (20 micrograms, Months 0, 1 and 6) was investigated in 23 Down's syndrome patients and compared to that in 30 other mentally retarded patients and 32 staff members. About 90% of Down's syndrome and other mentally retarded patients and 100% of staff members had anti-HBs at Month 9, but anti-HBs less than 10 IU per liter were found in 6/23 (26.1%) of Down's syndrome, 7/30 (23.3%) of other mentally retarded patients, in contrast to 2/32 (6.2%) of staff members. No differences in anti-HBs response with regard to sex and age were observed in staff members, but geometric mean titers of anti-HBs were lower in older Down's syndrome and other mentally retarded patients, and in male Down's syndrome patients. Supplementary vaccination is necessary in these individuals to obtain "protective levels" of anti-HBs.