Combination chemotherapy consisting of hexamethylmelamine, adriamycin, and cis-dichlorodiammineplatinum(II) was given to 27 patients with advanced epithelial ovarian cancer whose disease had progressed while receiving therapy including alkylating agents. Eighteen patients (67%) had objective partial or complete remissions for a projected median duration of 7 months. Based on this high level of activity in this poor-risk group, the three drugs were combined with cyclophosphamide in a four-drug regimen (CHAD) for initial therapy suitable for outpatient administration. Nineteen of 21 evaluable patients (90.4%) receiving CHAD responded. Complete clinical remissions were noted in ten patients (47.6%) and were confirmed at "second-look" laparotomy in two of these. An additional five patients without evaluable disease after initial surgery are free from relapse at 4--15 months. Toxicity was only moderately severe; 28% of the patients had wbc counts less than 2000/microliters at some point. Nephrotoxicity from cis-dichlorodiammineplatinum(II) was almost completely prevented by a 2-hour outpatient regimen of hydration and diuresis. A prospective randomized trial is planned comparing CHAD to melphalan in previously untreated women with advanced ovarian cancer.