In an effort to examine the potential clinical utility of intraperitoneal (i.p.) therapy in the management of patients with malignant peritoneal mesothelioma, 19 individuals with this disease were treated with a cisplatin-based i.p. treatment regimen. All but 1 patient also received i.p. mitomycin. The treatment was generally well tolerated, although a maximum of only four or five courses of cisplatin (100 mg/m2 every 28 days) and mitomycin (5-10 mg/treatment given 7 days after each i.p. cisplatin administration) could be administered, the treatment principally being stopped because of disease progression or catheter failure. Of 15 patients with malignant ascites, 7 (47%) experienced control of fluid reaccumulation ranging from 2 months to 73+ months (median 8 months). While the median survival for the 19 patients was only 9 months, 4 (21%) patients survived for more than 3 years from the initiation of therapy, and 2 patients are currently alive and clinically disease-free more than 5 years from the start of the i.p. treatment program. We conclude that a subset of patients with peritoneal mesothelioma, principally those with small-volume residual disease following surgical tumor debulking, can benefit from a cisplatin-based i.p. treatment strategy with control of ascites and prolonged disease-free survival.