Advanced or metastatic melanoma responds poorly to chemotherapy, which has no impact on survival. Responses have been recorded using cisplatinum as a single agent. This study tested the established combination of cisplatinum 100 mg/m2 and 5-fluorouracil 1 g/m2/day continuously intravenously for 5 days repeated every 3 weeks in patients with disseminated melanoma. Twenty-nine patients, 13 having received no prior systemic chemotherapy, received 49 cycles of therapy (median 1, range 1-4). Only one previously untreated patient achieved a partial response with a failure-free survival of 6.5 months and an overall survival of 7.7 months from the commencement of therapy. The major toxicities were nausea and vomiting, (grade 3 in eight patients), stomatitis (grade 4 in two patients, grade 3 in two patients), and myelosuppression. The study showed that cisplatin and 5-fluorouracil have a low order of activity in patients with advanced or disseminated melanoma.