The multimodality treatment of adenocarcinoma of the pancreatic head has been shown to improve survival compared with surgery alone. The delivery of chemotherapy and radiation therapy (chemoradiation) before rather than after pancreaticoduodenectomy ensures that all patients who undergo surgery receive the other components of multimodality therapy. In an effort to reduce overall treatment time and cost, the use of rapid-fractionation preoperative chemoradiation was explored. Radiation therapy was delivered with 18-MeV photons to a total dose of 30 Gy given in 10 fractions over 2 weeks. 5-Fluorouracil was given concurrently by continuous infusion at a dose of 300 mg m-2 day-1. Four weeks after the completion of chemoradiation, patients underwent pancreaticoduodenectomy and electron-beam intraoperative radiation therapy (10 Gy). All patients completed the treatment programme without delay. The rapid-fractionation programme was delivered at nearly half the cost of standard chemoradiation and histologic evidence of tumour cell injury was present in all resected specimens. There were no perioperative anastomotic complications, and median hospital stay was 20 days. Rapid-fractionation chemoradiation warrants further study in the neoadjuvant setting.