At the change from unheated to heat-treated Factor VIII concentrates for the treatment of hemophilia A, 17 severe adult hemophiliacs (mean monthly dose, 4927 IU) were evaluated prospectively for signs of infection with human immunodeficiency virus (HIV). Viral serology and lymphocyte subpopulations (OKT3, OKT4, and OKT8-positive cells) were examined monthly for 1 year. One patient seroconverted for HIV in the enzyme-linked immunoabsorbent assay but was positive on the Western blot analysis from the outset. There was a slight but significant increase in OKT4+ cells and OKT4/OKT8 ratio. These data suggest that heat-treated Factor VIII concentrates even when used in large amounts have a low risk of transmitting HIV.