Forty-two previously untreated patients with metastatic malignant melanoma were randomized to receive DTIC at a dose of 250 mg/m2/day 4 IV on days 1-5 or the same drug plus epirubicin (Epi-DX) at a dose of 90 mg/m2 on day 1. Cycles were repeated every 3 weeks. Partial responses were observed in two out of 22 patients (9.1%) treated with DTIC, and in four out of 19 evaluable patients (21.1%) treated with Epi-DX + DTIC. Overall, Epi-DX + DTIC combination was well tolerated, thus permitting administration after a 3-week interval of the full drug dosages in all but two patients. No major cardiotoxicity was observed. Although patients in the Epi-DX + DTIC group had a better response rate than those in the DTIC group, the difference was not statistically significant, and the 21.1% response rate observed with the two-drug combination does not differ from that reported with DTIC used alone.