Twenty-one patients with malignant mesothelioma were treated with an experimental intracavitary chemotherapy regimen of weekly intraperitoneal or intrapleural cisplatin (90-100 mg/m2) with simultaneous intravenous sodium thiosulfate delivered to protect against cisplatin-induced nephrotoxicity. One of eight patients (12.5%) receiving intrapleural therapy and nine of 13 patients receiving intraperitoneal therapy demonstrated objective evidence of a clinical response, including three surgically defined major tumor regressions (23%). Patients receiving intrapleural treatment had more advanced disease prior to therapy than those receiving intraperitoneal therapy. It was concluded that intraperitoneal cisplatin is an active treatment program for intra-abdominally localized mesothelioma. Additional investigation of intrapleural cisplatin should be undertaken in a patient population with less advanced disease or following surgical debulking.