Twelve patients ages 37-85 years (mean, 59 years) with locoregionally advanced vulvar carcinoma were treated with a combination of irradiation and chemotherapy using prolonged continuous infusions of 5-fluorouracil (5-FU) and cisplatin. Eleven patients had advanced vulvar disease with tumors 5-18 cm in maximum diameter (mean, 8.7 cm), eight had palpable inguinal nodes with biopsy-proven metastatic carcinoma, and five had fixed nodes. Patients received weekly 96-hr infusions of cisplatin (4 mg/m2/day) and 5-FU (250 mg/m2/day) for a total of 64 mg/m2 of cisplatin and 4 g/m2 of 5-FU in 4 weeks. Concurrent radiation therapy was delivered to the lower pelvis, vulva, and inguinal nodes to a total dose of 40-50 Gy at 2 Gy per fraction in 11 patients. One patient who had been previously treated for cervical cancer received radiation only to the vulva with an appositional electron beam field. Chemoradiation was well tolerated with virtually no hematologic toxicity and no unscheduled breaks in treatment. Eleven of 12 patients had at least a partial clinical response; one patient had a minimal response of unresectable vulvar disease. Of eight patients who underwent vulvar resection 6 weeks after chemoradiation, four had no residual disease in the resected vulvar specimen and remain disease-free 17, 20, 25, and 37 months, respectively, after surgery. Another patient is disease-free 28 months after a complete clinical response without vulvar resection. However, of four patients who had residual disease in the vulvar surgical specimen, disease has recurred within the irradiation field in three. Overall, 6 of 12 patients treated with this chemoradiation regimen remain disease-free 17-30 months after treatment. This is a well-tolerated outpatient regimen that yields a high response rate in patients with massive vulvar carcinomas.