"Natural" antibody titres to E. coli O antigens of different serotypes and to rabbit red blood cells were determined in 86 subjects with Down's syndrome and 79 mentally retarded but chromosomally normal controls ranging in age from 10 months to 52 years. Subjects in the two groups were matched for sex, age and socio-environmental conditions. Titres of both antibodies, assessed by haemagglutination, were significantly lower in subjects with DS in the 1 to 5 year old group. E. coli antibodies transiently increased to normal values in subjects with DS during the second 5 years of life, thereafter rapidly declining to levels significantly lower than those observed in controls. The titres of antibodies to rabbit erythrocytes in subjects with Down's syndrome showed a more variable course transiently approaching normal values in the 7-10 year group and after 20 years of age. These data are interpreted as further evidence for the existence of a congenital immunodeficiency in Down's syndrome.