Twenty-six patients with measurable metastatic melanoma were treated with estramustine phosphate (12 mg/mg body wt) orally every day. Tumor biopsies were assessed for estrogen receptors (ER) in 14 patients and for estramustine binding sites (EMBS) in 13 patients. ER and EMBS were measured with isoelectric focusing in polyacrylamide gels. Three partial responses (PR) (12%) and three no changes (NC) (12%) according to WHO criteria were registered. In one patient with NC and in four patients with progressive disease (PD) the tumors were ER positive. EMBS was found in one patient with PR and in two patients with PD. Because of the low frequency of antitumor activity and the low number of patients with ER and/or EMBS the number of patients is too low for any correlation between tumor response and ER and/or EMBS status.