We evaluated the response to therapy and outcome in patients with HIV-associated KS. Eighteen of 26 patients with newly diagnosed KS were treated continuously with IFN until progression of the disease occurred. In most patients with progressive disease, chemotherapy, usually with vinca alcaloid derivatives was instituted. Results were disappointing: 10 of 26 patients (38.5%) died after a median follow-up period of 4.5 months. Survival was shortest in patients who developed opportunistic infections, malignant lymphoma, or had a low OKT4/OKT8 ratio. Only one patient showed a complete remission and one patient had a partial remission under IFN therapy. Five additional patients had stable disease. Chemotherapy was without measureable effect on KS in patients who had progressive disease under IFN. IFN therapy was associated with various, not life-threatening adverse effects and was best tolerated by patients with a low OKT4/OKT8 ratio. Our results indicate that only a small portion of AIDS patients with KS seem to benefit from a continuous treatment with IFN.