This study was undertaken to evaluate the efficacy of a regimen of combined chemoradiotherapy in patients with unresectable adenocarcinoma of the pancreas. An analysis was undertaken on 27 patients from January 1992 to May 1996. Patients had a median age of 70 years (range, 40-78) and Eastern Cooperative Oncology Group Performance Status of 0-2. Eighteen patients had locoregional disease (T-2-T-3, N-0-N-1, M-0), and nine had metastatic disease. Chemotherapy consisted of four cycles of 5-fluorouracil 1 gm/m(2)/day as a continuous infusion over 110 hours, streptozotocin 300 mg/m(2)/day over 30 minutes on days 2-4, and cisplatin 100 mg/m(2) over 2 hours on day 4 only, followed by a maintenance regimen of 5-fluorouracil and leucovorin every 2 weeks. The radiotherapy was administered as a split course concurrently with chemotherapy to a total dose of 6000 cGy. Toxicity was frequent, but there were no treatment-related deaths. Grade III and IV toxicity was primarily limited to myelosuppression, stomatitis, and gastrointestinal side effects. Fifteen patients (56%) were able to complete either three or four cycles of chemoradiotherapy. All patients were evaluable for toxicity, response, and survival. Nine patients (33%) had an objective response (four complete response 5 partial response), two remained stable, and 16 (59%) had disease progression. Median survival for the entire group was 19 weeks (2-139), and the median survival for overall responders was 56 weeks (15-139), No patient with localized disease underwent subsequent surgical resection. The authors conclude that those patients who are able to tolerate the entire treatment regimen may achieve a useful prolongation of time to tumor progression.