BACKGROUND The authors sought to evaluate survival of patients with ovarian cancer treated with second-line intraperitoneal cisplatin-based chemotherapy. METHODS From August 1985 to September 1991, 63 patients with recurrent or persistent ovarian cancer after first-line cisplatin-based chemotherapy were on a protocol and treated with cisplatin, cytarabine, with or without bleomycin. Eligibility included Stage III/IV invasive adenocarcinoma of the ovary, documentation of the size of residual disease at reoperation, and prior treatment with first-line intravenous cisplatin-based chemotherapy. RESULTS The median survival from intraperitoneal chemotherapy was 29 months. For patients who responded to first-line chemotherapy and second-line intraperitoneal chemotherapy, the 5-year survival was 60%, but for patients with response to first-line chemotherapy but no response to intraperitoneal chemotherapy the 5-year survival was only 17%, and no patient survived 5 years who did not have a response to first- or second-line therapy (P < 0.0001). There was significant improvement in the 2-year survival from initiation of intraperitoneal chemotherapy for patients with < or = 5 mm residual tumor in greatest dimension (74%), compared with patients with residual tumor larger than 5 mm and smaller than or equal to 2 cm (38%), and patients with residual tumor larger than 2 cm (0%) (P < 0.0001). CONCLUSIONS Survival was increased for patients who (1) had a response to first-line intravenous chemotherapy and second-line intraperitoneal chemotherapy and (2) who had residual tumor 5 mm or smaller at the initiation of intraperitoneal therapy. The conclusion that the prolonged survival is secondary to cisplatin-based chemotherapy administered intraperitoneally must be made with caution because survival may have been secondary to the small residual disease at initiation of second-line chemotherapy or the systemic effect of cisplatin.