The purposes of this study were to determine whether continuous infusion of fluorouracil combined with external-beam radiation therapy improved the resectability and survival of patients with pancreatic carcinoma. Sixteen patients with unresectable disease confined to the pancreas and celiac nodes were treated, and their outcome was compared with that of 24 patients with potentially resectable disease who were treated concurrently. The neoadjuvant therapy was completed with acceptably few toxic effects but with only a minor decrease in tumor size. Two patients underwent resection and remained free of disease 20 and 22.5 months later. However, the median survival of the entire neoadjuvant group was 8 months. All 24 patients with potentially resectable carcinoma underwent surgical exploration. Fifteen of the 24 patients underwent resection and survived a median of 12.5 months. Neoadjuvant chemoradiation may have improved outcome and resectability for two (12.5%) of 16 patients with unresectable pancreatic carcinoma, but more effective therapy options must be developed to improve outcome.