Objectives.In an effort to critically examine the antitumor activity of altretamine (hexamethylmelamine) as salvage therapy of platinum-refractory ovarian cancer, the Gynecologic Oncology Group initiated a Phase II trial of the agent administered in this clinical setting.Methods.Altretamine was administered at a dose of 260 mg/m 2 orally for 14 days in a 28-day course. Treatment was continued until disease progression or unacceptable side effects prevented further therapy. A total of 36 patients (median age: 56.5) were treated on this trial, of whom 33 were evaluable for toxicity and 30 for response. All patients had previously received either cisplatin or carboplatin and paclitaxel.Results.The major side effect was emesis (grade 3–4,733, 21%). The objective response rate was 10% (one complete response, two partial responses).Conclusion.We conclude that altretamine has limited activity in platinum-refractory ovarian cancer.