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We investigated the relationship of the presence of antibodies to HTLV-III and immunologic abnormalities in patients with hemophilia. Serum antibodies to HTLV-III were analyzed by ELISA assay, immunoprecipitation of labeled cell extracts, and immunoprecipitation of purified HTLV-III p24. Thirty-four (61%) of the total group (n = 56) had antibody to HTLV-III; 34 (76%) of 45 patients given commercial factor VIII preparations were seropositive, compared with none of 11 patients treated exclusively with cryoprecipitate obtained from volunteer blood donors. Of patients who were seropositive for HTLV-III antibody, 94% had abnormal T4/T8 ratios, and 33% of those whose serum was antibody negative had abnormal T4/T8 ratios; five patients, each antibody positive, have lymphadenopathy syndrome. Sequential studies in a subset of patients indicate that there is a changing pattern of antibody production to HTLV-III antigens after seroconversion.