A phase II study of ip 5-FU was performed in 14 patients with ovarian cancer who were refractory to systemic chemotherapy including prior iv 5-FU in 12 of the patients. 5-FU was administered via a semipermanent Tenckhoff peritoneal dialysis catheter. The starting concentration of 5-FU in the dialysate was 4 mM. The patients received eight consecutive 2-L exchanges, each of 4-hour duration, for a total of 36 hours including time for instillation and drainage. Treatment courses were repeated every 2 weeks for six cycles or until disease progression occurred. A total of 69 cycles of ip 5-FU were administered to 14 patients. There was one complete response to therapy documented by second-look laparotomy. While the response rate was only 7%, in seven of eight (88%) patients with small volume disease (tumor masses less than 2.0 cm in diameter), there was no evidence for disease progression while receiving ip 5-FU therapy. In this phase II trial, the major toxic effect of ip 5-FU was abdominal pain. While there were no cases of documented bacterial peritonitis, all of the patients experienced some degree of abdominal discomfort while receiving therapy. Fifty percent of the patients had severe abdominal pain with at least one cycle of therapy. Other toxic effects included myelosuppression, mucositis, nausea and vomiting, and skin rash. The results of this study indicate that ip 5-FU should be further evaluated in patients with ovarian cancer who have a small volume of disease and who have not had prior therapy with 5-FU.