An epidemic form of Kaposi's sarcoma associated with the acquired immune deficiency syndrome has been recently described. Seven homosexual men with biopsy-documented epidemic Kaposi's sarcoma were treated with a human interferon-gamma preparation. All patients had generalized disease. Only one patient had received prior chemotherapy, and one other patient had recovered from a prior opportunistic infection. Interferon-gamma was administered in a dose of 500,000 U intramuscularly daily, with two 10-day induction courses, separated by a 2-week medication-free period. This was followed by maintenance therapy in the same dose twice weekly. Toxicities consisted of a flu-like illness with high fevers, shaking chills, myalgias, and arthralgias. There were no complete or partial responses. All patients exhibited disease progression, with a rapid progression of previously stable disease necessitating discontinuation of therapy in three patients. We conclude that low doses of this human interferon-gamma preparation are ineffective in epidemic Kaposi's sarcoma.