Melanoma patients with very advanced disease are usually excluded from chemoimmunotherapy trials; however, the efficacy of intensive treatment regimens needs to be established for this patient population. This study aimed to evaluate the response rate and survival achieved with chemoimmunotherapy in very advanced melanoma patients. Forty-two patients received dacarbazine (250 mg/m2, days 1-3), cisplatin (30mg/m2, days 1-3), interferon-alpha (10 Mio IU/m2 subcutaneously, days 1-5) and intravenous interleukin-2 (18 Mio IU/m2 over 6 h, 12 h then 24 h, followed by 13.5 MioIU/m2 in 72 h). In cases of brain metastases (n = 12) radiation therapy was added. Ten patients (24%) achieved a partial response, 11 (26%) had stable disease and 21 (50%) had disease progression in an intention-to-treat analysis. The median overall survival of patients with a partial response or stable disease was 9 months in contrast to 3.5 months in patients with disease progression. Normal serum lactate dehydrogenase before the start of treatment was a strong favourable prognostic marker for survival (P< 0.002). We conclude that the described treatment schedule offers safe palliation in patients with very advanced metastatic melanoma.