Aims and Background This trial evaluated the feasibility and tol-erability of an immunochemotherapeutic approach that uses cisplatin, vindesine, and dacarbazine (DTIC), or only DTIC, in combination with interferon alpha-2a (IFN-a), in patients with metastatic melanoma, considering the significant toxicity of several different regimens used up to now. Methods Between May 1995 and September 1997, 51 melanoma patients (50 of whom were assessable) entered a multicentric trial and were randomized to receive cisplatin (30 mg/m² daily for 3 days) + vindesine (2.5 mg/m² only day 1) + DTIC (250 mg/m² daily for 3 consecutive days) + IFN-α (3 MIU im 3x/wk continuously) (CVD arm) versus DTIC (800 mg/m² day 1) + IFN-α (3 MIU im 3x/wk continuously) (DTIC arm). The chemotherapy was recycled every 21 days. Patient reevaluation was performed every two cycles, and the treatment was continued in case of objective response or stabilization of disease. Results We observed 3 complete responses, 2 partial responses and 5 stable diseases in the CVD arm, and 2 partial responses and 4 stabilizations of disease in the DTIC arm. Conclusions We conclude that these chemotherapeutic regimens are well tolerated regimens with modest toxicity. Future trials will be conducted associating the CVD regimen with biological response modifiers (IFN, IL-2) in order to improve the results.