Hypergammaglobulinemia is a consistent finding in patients within the AIDS spectrum and with hemophilia A. Serum samples from patients with these conditions were analyzed for the presence of oligoclonal banding, using a high-resolution serum protein electrophoresis system. The incidence of banding is significantly greater in well homosexuals who are HIV-antibody positive and in patients with pre-AIDS-related complex, AIDS-related complex, AIDS with opportunistic infections, and AIDS with Kaposi's sarcoma than in normal blood donors. The incidence of banding is similar to controls in patients with hemophilia who have received either no blood products, cryoprecipitate only, or limited infusions of factor VIII concentrate. In patients who have received frequent infusions of factor VIII concentrate, the incidence of banding significantly increases. Thirteen of sixty-seven hemophiliac patients developed AIDS or symptoms related to HIV infection independent of their banding pattern. We hypothesize that the bands are not diagnostic of AIDS, but seem to correspond with disease progression, and that they are absent early in the disease, appear later in the course, and may disappear with advanced disease.