Forty patients with stage III or IV epithelial ovarian tumors were treated with a combination of hexamethylmelamine, cyclophosphamide, methotrexate, and 5-fluorouracil. Fourteen of 37 evaluable patients had recieved previous treatment. Three of these 14 previously treated patients responded; no complete remissions were achieved and more severe toxicity was seen compared with the 23 previously untreated patients. In the latter group of patients, seven partial remissions and five complete remissions documented by peritoneoscopy and laparotomy were achieved. It is concluded that the combination of hexamethylmelamine, cyclophosphamide, methotrexate, and 5-fluorouracil is not useful as second-line chemotherapy but can be considered suitable for remission induction in previously untreated patients.