Four-hundred twenty-six patients with disseminated melanoma were analyzed, all of whom were treated with chemotherapy. There was a high correlation with hepatic metastases and elevated lactic dehydrogenase levels. Although there were frequent false-positive lactic dehydrogenase levels, normal lactic dehydrogenase levels were consistently associated with a normal liver. Central nervous system disease was a major cause of morbidity and mortality in metastatic melanoma. Eleven % of the patients in this study had evidence of central nervous system disease at onset. The only treatment that was proven to be effective in these patients was whole-brain radiotherapy with concomitant dexamethasone administration. There were certain areas of anatomical involvement that correlated with an improved survival. These were patients that had pulmonary metastases only (median survival, 10 months) and patients with disease limited to the skin and S.C. tissue (median survival), 11 months). The median survival for all patients was 4.7 months. The response rate to a variety of treatment regimens with 5-(3, 3-dimethyl-1-triazeno)imidazole-4-carboxamide was 18% (75 of 426) for all patients and 23% for evaluable patients only. There was an increased response to 5-(3, 3-dimethyl-l-triazeno)imidiazole-4-carboxamide for nonvisceral involvement (28%), compared with visceral involvement (13%). The addition of l, 3-bis[2-chloroethy 1-1-nitrosourea appeared to have an increased response rate for pulmonary and other visceral involvement, compared with 5-(3, 3-dimethyl-l-triazeno)imidazole-4-carboxamide alone. © 1974, American Association for Cancer Research. All rights reserved.