We report the results of a multi-institutional phase II trial that used preoperative full-dose gemcitabine and radiotherapy for patients with potentially resectable pancreatic carcinoma. Patients were treated before surgery with three cycles of full-dose gemcitabine (1000 mg/m2 intravenously), with radiation during the second cycle (36 Gy in daily 2.4-Gy fractions). Patients underwent surgery 4 to 6 weeks after the last gemcitabine infusion. There were 10 men and 10 women, with a median age of 58 years (range, 50-80 years). Nineteen patients (95%) completed therapy without interruption, and one experienced grade 3 gastrointestinal toxicity. The mean weight loss after therapy was 4.0%. Of 20 patients taken to surgery, 17 (85%) underwent resections (16 pancreaticoduodenectomies and 1 distal pancreatectomy). The complication rate was 24%, with an average length of stay of 13.5 days. There were no operative deaths. Pathologic analysis revealed clear margins in 16 (94%) of 17 and uninvolved lymph nodes in 11 (65%) of 17 specimens. One specimen contained no residual tumor, and three specimens revealed only microscopic foci of residual disease. With a median follow-up of 18 months, 7 (41%) of the 17 patients with resected disease are alive with no recurrence, 3 (18%) are alive with distant metastases, and 7 (41%) have died. Preoperative gemcitabine/radiotherapy is well tolerated and safe when delivered in a multi-institutional setting. This protocol had a high rate of subsequent resection, with acceptable morbidity. The high rate of negative margins and uninvolved nodes suggests a significant tumor response. Preliminary survival data are encouraging. This regimen should be considered in future neoadjuvant trials for pancreatic cancer.