HLA typing was performed on lymphocytes from patients with a disease or from families where more than one individual had a common disease type. HLA typing was performed in a cohort of individuals with acquired immune deficiency syndrome (AIDS), either Kaposi's sarcoma, or opportunistic infections, or individuals at risk for this disease. A total of 250 individuals have been HLA typed. One hundred of these patients have been followed over a 4- 5 year period. The objectives of these studies are to examine possible genetic susceptibility to the development of AIDS or AIDS- related complex that is related to expression of histocompatibility antigens. The HLA-DR1 phenotype is increased in frequency in all AIDS patients compared to human immunovirus (HIV)-seropositive controls. HLA-DR3 is significantly decreased in the patients with Kaposi's sarcoma. In the HIV-seropositive individuals followed for 65 months, HLA-DRI appears to be a specific risk factor for disease development. Three families with more than one member with acute lymphocytic leukemia were analyzed for DNA polymorphism in the HLA- DQB genes. Common restriction patterns were found in the leukemic individuals. Sera from 30 hemophiliacs (10 developed AIDS, 10 HIV- seropositive AIDS free and 10 HIV-seronegative) were obtained prior to seroconversion and subsequent yearly samples were tested for antibodies to HLA antigens. Individuals developing AIDS demonstrated increased reactivity to a range of HLA antigens, while losing total CD4+ cells.