Twenty-three patients with advanced gynecologic malignancy were treated with definitive irradiation and synchronous sensitizing chemotherapy (CT) consisting of cisplatin (CDDP), 50 mg/m2 i.v. rapid infusion, and a 5-day continuous infusion of 5-fluorouracil (5-FU), 750 mg/m2/day. A total of three cycles were administered every 3-4 weeks. Fifteen patients had primary cervical epidermoid carcinoma (three bulky stage IIB, one stage IIIA, ten stage IIIB, one stage IV), four had pelvic recurrences of carcinoma of the cervix, two had endometrial adenocarcinomas (stage IV), and two had vulvar epidermoid carcinoma (one stage III and one stage IV). Radiotherapy (RT) for implantable tumors consisted of 2,000 cGy whole pelvis, 3,000-4,000 cGy split field, and two intracavitary or interstitial insertions, resulting in a total dose of 7,500-8,000 cGy to point A. Three courses of CT were delivered simultaneously with irradiation of the central bulk of tumor: during the first week of whole pelvis RT and with each of the two brachytherapy procedures. Nonimplantable tumors were treated with protracted external beam RT (5,500 cGy tumor dose) and three courses of CT during weeks 1, 4, and 7 of RT. Twenty-one of 23 patients completed RT and 18 of 23 patients completed CT as planned, but half had delays in either RT or CT. Grade 2 or 3 late sequelae consisted of leg edema (one patient), proctosigmoiditis (one patient), bowel obstruction (one patient), vesicovaginal fistula (one patient), and pulmonary embolus (two--one fatal). The incidence of grade 2 and 3 sequelae were 18 and 22%, respectively. With 1-3 years of follow-up evaluation, 12 of 23 (52%) patients are free of disease, and 9 of 22 evaluable patients (41%) have had failure within the pelvis. We conclude that high-dose definitive RT can be delivered with synchronous CDDP and 5-FU at the doses given, with acceptable toxicity. Further study is required to evaluate the impact of radiosensitization on tumor control and late morbidity of therapy. Optimization of irradiation and drug doses as well as the best schedules that may enhance the interaction of these two modalities should be further investigated.