Interleukin-6 (IL-6) levels were determined in the serum of 14 HIV-1-infected patients with Kaposi's sarcoma, 10 HIV-1-infected patients without symptoms, and 10 healthy male subjects. IL-6 levels were also determined in the serum of the 14 patients with Kaposi's sarcoma during treatment with high-dose human recombinant interferon-alpha (IFN alpha). Serum IL-6 levels were significantly higher in the patients with Kaposi's sarcoma than in the HIV-infected patients without symptoms and the controls. There was no consistent pattern of changes of IL-6 levels during IFN alpha treatment. These results support the view that IL-6 is a cytokine involved in the pathogenesis of AIDS-associated Kaposi's sarcoma, but appear to argue against an effect of IFN alpha on the production or release of IL-6 as an important mechanism of action of IFN alpha.