Immunoglobulin levels in institutionalized patients and outpatients with Down's syndrome were compared with the levels found in age- and sex-matched institutionalized and noninstitutionalized patients with other forms of mental retardation. The significant findings were the following: (1) elevated γG levels in institutionalized Down's syndrome patients, (2) very low γM levels in Down's syndrome outpatients, and (3) no significant differences in γA levels. These results are interpreted as suggesting an intrinsic immunologic defect in Down's syndrome causing the low γM levels in outpatients, and an acquired environmental factor (or factors) causing the elevated γG level in inpatients. Viral infections acquired in institutions, and persisting because of the intrinsic defect, are suggested as the responsible factors. The Australia antigenassociated viral hepatitis is one such infection which fits this hypothesis.