Children with hemophilia A are at risk for the acquired immunodeficiency syndrome (AIDS). Clinically asymptomatic hemophiliacs demonstrate many immune abnormalities that might represent exposure to the AIDS agent through blood products or be a natural reaction to their therapy. In this study, we examined lymphocyte subset distribution in children with hemophilia A who had been exposed to HTLV-III as determined by antibody seroconversion. Seroconversion to HTLV-III was confirmed using Western blot analysis. The lymphocyte subsets studied included T4+ and T8+ cells. The distribution of lymphocyte subsets in children with hemophilia A was independent of seroconversion to HTLV-III. Children with hemophilia A treated with commercial factor VIII concentrate had normal numbers of circulating T4+ lymphocytes and significantly increased numbers of circulating T8+ lymphocytes compared with their nontransfused age-matched counterparts. An increased number of T8+ lymphocytes was not observed, however, in children treated exclusively with cryoprecipitate. These results suggest that HTLV-III alone cannot account for changes in lymphocyte subsets in hemophiliacs. Higher antigenic protein loads in factor VIII concentrate or additional factors might account for the increased absolute numbers of T8+ lymphocytes and represent a natural response to therapy.