A comprehensive study was initiated to examine the immunologic status of a sample (n = 47) of the asymptomatic hemophilia A and B populations of metropolitan Atlanta and to determine if any of the abnormalities changed with time or correlated with infection by human T cell leukemia virus type III and lymphadenopathy-associated virus (HTLV-III/LAV) or other viruses either alone or in combination. Patients with hemophilia A (Hem-A) showed a defect in cellular immunity evidenced by a depressed T cell helper/suppressor ratio (P less than .0001), an increased absolute T suppressor cell number (P less than .0001), and a diminished number of T helper cells (P = .003) when compared with health professionals. Lymphocytes from these patients also showed a reduced ability to transform in response to phytohemagglutinin and pokeweed mitogen. No deterioration in immune status was seen during a median ten- month period of follow-up. Sixty-four percent of Hem-A patients had antibodies to HTLV-III/LAV and those who were seropositive had a significantly decreased helper/suppressor cell ratio (P = .018) and a diminished T helper cell number (P = .002); they were also more likely to have had exposure to cytomegalovirus than HTLV-III/LAV-negative Hem- A patients (P = .016). Heavy use of factor VIII concentrate was associated with a decreased number of T helper cells (P = .037) and seropositivity for HTLV-III/LAV (P = .011 in 1982). Hemophilia patients had higher IgG, immune complex, and beta 2-microglobulin levels than health professionals (P less than .0001). Although the most prominent abnormality observed in T cell subsets of patients with hemophilia is an increase in T suppressor cells, a finding likely to be associated with immune augmentation in response to multiple stimuli, the T cell abnormality that was predictive of exposure to HTLV-III/LAV, the putative acquired immunodeficiency syndrome agent, was a diminished number of T helper cells.