Twenty-two patients with recurrent ovarian cancer were entered into a Phase II trial of edatrexate at a dose of 80 mg/m2 i.v. weekly for five consecutive weeks. One patient received an inadequate trial, and six did not complete one cycle due to adverse effects. There were 21 patients evaluable for toxicity and 15 for response. There were no objective responses, 10/15 (67%) had stable disease, 5/15 (33%) increasing disease. Toxicity was predominantly stomatitis and hematologic. Two patients developed skin rashes, and one experienced pulmonary toxicity felt to be related to the drug. Edatrexate administered in this dose and schedule has no demonstrated activity, but moderately severe toxicity in patients with previously treated advanced ovarian cancer.