In order to determine whether preresectional chemoradiotherapy (CTRT) would influence resectability, local control, and survival of patients with localized pancreatic adenocarcinoma, a 5 1/2-year prospective study of 39 patients treated with preoperative radiation therapy, 5-Fluorouracil (5-FU), and Mitomycin C has been performed. Thirty patients had celiotomy after CTRT (1/39 died while receiving CTRT, one refused surgery, and seven had extrapancreatic disease progression). Seventeen (57%) had resections (seven total, two distal subtotal, and eight Whipple pancreaticoduodenectomies). All had clear margins of excision, and only one had any positive lymph nodes in the resected specimen. Eleven patients with resection had Stage I cancers (5 T1b, 6 T2), five had Stage II, and one had a Stage III lesion. Previous bypass surgery, age, clinical response to CTRT, and tumor size had no influence on resectability. Two patients died postoperatively (12%) early in the series. Three others suffered major morbidity (chylous ascites requiring peritoneovenous shunt, ARDS, and prolonged afferent loop obstruction leading to a fatal liver abscess 5 months after surgery). Two patients with resection are alive without recurrence at 48 months after tissue diagnosis, and six others are also alive without recurrence, after from 6 to 23 months. In summary, resectability is probably enhanced and nodal metastases and resection margins are downstaged by preoperative CTRT. Demonstration of an improved survival benefit awaits further observation and phase III trials.