Between June 1981 and June 1984, 50 patients with stage III or IV epithelial ovarian cancer underwent initial surgery followed by combination chemotherapy with cisplatin 50 mg/m2 iv and cyclophosphamide 500-1000 mg/m2 iv at 28-day intervals. No patients with borderline or well-differentiated tumors were included. If patients were clinically disease-free after 12 cycles of therapy, a second-look laparotomy was performed. A complete response was noted in 12 patients (24%), 11 of whom were surgically evaluated. A partial response was noted in 4 patients (8%), 3 of whom were surgically evaluated. Thirty-four patients (68%) had no response to therapy. The median progression-free survival (PFS) for the entire group was 19.8 months, with a median survival of 27 months. Patients with less than or equal to 2 cm residual disease had a superior median PFS (25.4 months vs 18 months) and median survival (29.4 months vs 19.5 months) to those patients with greater than 2 cm residual disease. Patients who underwent primary debulking had a longer median survival than patients who underwent "interval" debulking after two to four cycles of chemotherapy (29.2 months vs 17.3 months). Thirteen patients (26%) are alive without evidence of disease, 4 patients are alive with disease, and 33 patients are dead of disease. Toxicity was very moderate. In summary, the activity and toxicity of the combination of cisplatin and cyclophosphamide compare favorably to other cisplatin combination regimens.