Twenty-six patients (14 men and 12 women) with histologically proven advanced malignant melanoma, who previously had not responded to DTIC, methyl-CCNU, and procarbazine, received estramustine phosphate (estracyt) (15 mg/m2) in daily divided doses. All patients had measurable disease. One patient developed a complete remission and one patient had improvement in liver function without measurable regression in the tumor. In three other patients (11%), the disease remained static for a period of 3--5 months. The mean survival time from the beginning of therapy was 16.8 months for the patients with a response or static disease and 2.18 months for those who had no response. Gastrointestinal toxicity was minimal; no hematologic toxicity was observed. It appears that estramustine phosphate used as a single agent for treating advanced malignant melanoma after patients failed to respond to DTIC and to the combination of methyl-CCNU and procarbazine has a poor response rate.