The objective of this study was to evaluate the activity of the combination of 5-fluorouracil (5-FU) and leucovorin in women with platinum-resistant recurrent or advanced ovarian cancer. A retrospective study was conducted of consecutive patients treated with weekly intravenous 5-FU and leucovorin, both at 500 mg/m2. Sixty-one cycles were administered to 28 women between 1989 and 1995. The median age of the patients was 58 years and median number of previous chemotherapy regimens was 2. No patient had a complete response. There was 1 partial response (PR) among 8 patients with measurable disease, and 4 PR among 20 women with evaluable disease; 2 had stable disease and 21 progressed on treatment for a response rate of 18% (95% confidence interval, 3-33%). Duration of response was 2 to 14 months, median 5 months. Survival from the start of 5-FU/leucovorin ranged from 1 to 78 months, median 5.5 months, and a mean of 10 +/- 15 months (mean +/- SD). The combination of 5-FU/leucovorin had minimal activity in this patient population. Only 2 women achieved resolution of their ascites and experienced a significant palliation.