5-Fluorouracil (5-FU) is an antimetabolite chemotherapy, which selectively functions at the S phase of the cell cycle. It is a short-acting agent with a serum half-life of approximately 11 minutes. Increased efficacy with this drug could theoretically be provided by sustained infusion over the doubling time of a tumor. Ovarian cancer that recurs or persists after treatment with platinum-based chemotherapy has a poor prognosis. This study examines the use of long-term infusional 5-FU as a salvage chemotherapy for ovarian cancer. 14 patients with epithelial ovarian cancer were studied. All were stage III or IV disease and all were initially treated with platinum-based chemotherapy with either persistence or recurrence of disease. Patients received 5-FU as 300 mg/m2/day via a continuous infusion for a 10-week cycle with discontinuation occurring for severe toxicity or documented progression. The average infusion per patient was 8 weeks (3-10). Three patients had drug discontinued secondary to toxicity (severe mucositis) and 4 patients had progression prior to the completion of 10 weeks. All patients had progression by the end of the first cycle. The average survival post-5-FU was 8.9 months (range: 0.75-22 months). The lack of response in 14 patients indicates that, statistically, the likelihood of an overall response rate of 20% is less than 0.05. Infusional 5-FU appears to be ineffective as salvage therapy for ovarian cancer.