Twenty-five patients with advanced malignant mesothelioma were treated in a phase II trial with high-dose cisplatin (DDP). All patients had measurable or evaluable disease. Seven patients had received prior chemotherapy. DDP (120 mg/m2) with mannitol and prehydration was given every 4 weeks for two doses and then every 6 weeks. Of 24 patients evaluable for response, three had partial responses (3, 3+, and 9 months; response rate, 13%; 95% confidence limits, 4%-31%) and one had minor response. All responses occurred in previously untreated patients. High-dose DDP has modest activity in malignant mesothelioma.