The incidence of AIDS-associated Kaposi's sarcoma has declined since the mid-nineties due to the availability of potent antiretroviral therapy including protease inhibitors. However, Kaposi's sarcoma is still the most common neoplasia in HIV-infected patients. In the pathogenesis of the HIV-associated as well as other forms of this disease an infectious agent seems to play a role, namely the human herpesvirus 8. Even before the discovery of the HIV virus, high levels of an unusual acid-labile form of endogenous interferon alpha were found in patients with AIDS-associated KS. The administration of recombinant interferon alpha evolved as standard therapy for Kaposi's sarcoma in HIV-infected patients with a moderate immunodeficiency in addition to antiretroviral therapy. This investigation monitored the levels of HHV 8 and endogenous interferon in 4 patients with and without Kaposi's sarcoma during the course of HIV-disease. The results of our experiments lead us to two hypotheses: First of all, the pre-therapeutic level of endogenous interferon may be a predictor of the response to an interferon-alpha therapy for HIV-associated Kaposi's sarcoma. Secondly, the determination of HHV 8 DNA in blood of HIV-positive patients may allow conclusions about the risk for the development of Kaposi's sarcoma. However these hypotheses should be tested by monitoring the levels of endogenous interferon and HHV 8 DNA in clinical studies of a greater number of HIV-infected patients.