This report summarizes our experience in the treatment of advanced melanoma with immunotherapy and chemoimmunotherapy. A total of 45 patients initially received immunotherapy with interferon-alpha (IFN alpha) and a decrescendo regimen of high-dose interleukin-2 (IL-2). The objective response rate is 31% with an additional 36% of mixed response (MR) and stable disease (SD). A total of 18 patients failing immunotherapy with IFN-alpha/IL-2 received subsequent chemotherapy with dacarbacine (DTIC), followed by IFN-alpha. The response rate for this second-line regimen is 22%. A further 11 patients failing IFN-alpha/IL-2 received a single dose of DTIC or cisplatinum (CDDP) on day 1, followed by IFN-alpha/IL-2 according to the same protocol as previously, without chemotherapy. The addition of DTIC or CDDP was fairly well tolerated. Induction of secondary mediators was not inhibited, suggesting that the immunologic effects mediated by IL-2 are not impaired. A randomized clinical trial is now being performed to compare combined chemoimmunotherapy with immunotherapy alone.