Fifty previously untreated patients with advanced or recurrent ovarian cancer (FIGO Stages III and IV) were treated with alternating combination chemotherapy. This consisted of high-dose doxorubicin (70 mg/m2) and cisplatin (100 mg/m2) alternated with CHF (cyclophosphamide, hexamethylmelamine, and 5-fluorouracil). Toxicity (myelosuppression, nephropathy, and neuropathy) was infrequent and mild. Clinical response rates were high (94% response, 62% complete clinical response), but the majority of patients had residual intraabdominal disease at second-look surgery (75%). Thirteen patients (26%) are alive after 4 years of observation (minimum follow-up). Survival was adversely influenced in patients who were older than 70, had Stage IV disease, residual tumor bulk greater than 2 cm, and who failed to achieve complete clinical remission. The median duration of survival (28 months) and percentage of long-term survivors appear similar to that in other platinum-based chemotherapy studies. Although the role of alternating combination chemotherapy in epithelial ovarian cancer remains undefined, it is likely that an alternate approach will be necessary to markedly improve survival rates for patients with this disease.