Twenty-two patients with advanced malignant melanoma were entered in a pilot study receiving combination chemotherapy with PALA, vindesine, and cisplatin (PVP). Treatment consisted of PALA 3000 mg/m2 IV on days 1 and 2, vindesine 3 mg/m2 IV on days 1 and 8, cisplatin 30 mg/m2 IV on days 1 through 5, with treatment cycles repeated on day 21 every 3 weeks. Of 22 patients, 3 had non-visceral disease confined to iuxtaregional tumor growth (Stage III), and 19 had disseminated and/or visceral disease (Stage IV). The male/female sex distribution was 13/9; median age was 45 years. All 22 patients had measurable disease; 21 were evaluable for response and toxicity. Five patients (24%) had a complete response (CR) with a median duration of 5 months, and four patients (19%) had a partial response (PR) with a median duration of 3 months. Seven patients showed disease stabilization (33%) with a median duration of 2 months. Progressive disease was seen in five patients (24%) and was commonly due to widespread visceral disease. CR could be found predominantly in non-visceral disease, whereas PR could be observed in visceral disease also. Survival time from the onset of PVP chemotherapy cannot be estimated finally, since some of the responses are continuing at the present time, and 7 of 21 patients are still alive. Currently, median survival time for responders is 8 months, and for nonresponders, 5 months. Toxicity of PVP chemotherapy is mild to moderate and allows cytotoxic drug administration on an outpatient basis. PVP chemotherapy appears to have significant activity against malignant melanoma and may therefore be an alternative regimen in the management of advanced disease. However, despite the relative high remission rate especially in non-visceral disease, response duration remains disappointingly low.