The development of disseminated melanoma is associated with an extremely poor prognosis. Use of a variety of chemotherapy agents alone and in combination has yielded response rates of only 10-30%. Surgery and radiation therapy play a useful role in palliative treatment, but have little or no value in the treatment of disseminated disease. In order to evaluate the response of disseminated malignant melanoma to combination chemotherapy with cis-platinum and 5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide (DTIC), a phase II pilot study was developed and conducted at Oregon Health Sciences University. Thirty patients were treated from January 1983 to October 1986 and evaluated. There were two complete responses (7%) and nine partial responses (30%) for a total response rate of 37%. The median duration of response was 31 weeks. This response rate is higher than has been previously achieved with DTIC and cis-platinum, or with other drugs alone or in combination. Severe (grade 3) renal, neurologic, and hematologic toxicity was seen in four of 30, three of 30, and ten of 30 patients, respectively.