Twenty-two consecutive patients with bulky or locally advanced cervical or vaginal adenocarcinoma were treated with a neoadjuvant chemotherapy regimen consisting of nine weekly courses of cisplatin (50 mg/m2) and three courses of epirubicin (70 mg/m2) at Weeks 1, 4, and 7, followed by radical hysterectomy. Salvage radiotherapy was administered to inoperable patients, whereas postoperative treatment with irradiation or further chemotherapy was given to those with detection of risk factors at surgery. Three patients (14%) did not complete the planned courses of chemotherapy (one refused after the first administration, one had severe myelotoxicity, and one had severe nephrotoxicity). Twenty-one subjects received at least four courses of treatment and were therefore evaluable for response. We observed 4 clinically complete and 10 partial responses, accounting for an objective response rate of 67%. Eighteen subjects (82%) underwent surgery without serious complications. No histopathologic complete response was observed. The response rate is in the lower range observed with other regimens for squamous cell carcinoma. Although feasible, this regimen implies a significant risk of myelotoxicity. This enhanced toxicity may be justified only if balanced by long-term survival.