Five hundred three patients with advanced malignant melanoma were exposed to a number of clinical investigative chemotherapeutic regimens between 1971 and 1984 in an effort to assess the clinical activity of these regimens in this disease. Of the 503 patients participating in the studies, ten patients experienced a complete response. However, only three of these patients survived more than 5 years. Of this group of 503 patients, seven additional patients who did not experience a complete response survived more than five years. Of the ten patients surviving more than 5 years, two had immediate progression after institution of investigative regimens, whereas five remained stable for brief periods of time before progressive metastatic disease. Three patients experienced a complete response. It appeared that systemic therapeutic interventions in these trials were conspicuously ineffective for this large group of patients. A few long-term survivors attest to the capricious nature of this neoplasm and its association with likely spontaneous regressions. Although these long-term survivors did survive after institution of systemic chemotherapy, it is likely that this survival was related temporally, but perhaps not causally, to the institution of treatment.