UNLABELLED In locally advanced carcinoma of the exocrine pancreas combined radiochemotherapy has been established as a standard treatment. MATERIALS AND METHODS Two different treatment schemes have been consecutively used. Between 1/1994 and 12/2001, a total of 110 patients with locally advanced adenocarcinoma of the pancreas were treated with hyperfractionated accelerated radiotherapy to a total dose of 44.8 Gy combined with 5-fluorouracil (5-FU) (600 mg/m2) and folinic acid (FA) (300 mg/m2) injection. Chemotherapy was repeated monthly in non-progressive disease. From 1/2002 to 11/2003, in another 15 consecutive patients, chemotherapy was changed to gemcitabine (Gem) (300 mg/m2) and cisplatinum (Cis) (30 mg/m2), followed by gemcitabine (1000 mg/m2) every 2 weeks in non-progressive patients. RESULTS Median survival in the 5-FU/FA group was 10.3 months with a 1-year survival of 46.6% and a 2-year survival of 20.1%. Median time to progression was 8.6 months. Treatment was well tolerated with nausea/vomiting grade I/II in 58.2%, grade III/IV in 14.5%, diarrhea grade I/II in 27.3%, leucopenia/thrombopenia grade I/II in 21.8%, grade III/IV in 7.2%, and mucositis grade III/IV in 7.2%. In the Gem/Cis group, median survival was 13.8 months with a 1-year survival of 54.9% and a 2-year survival of 24.4%. The toxicity data also revealed comparable feasibility: nausea/vomiting grade I/II in 46.7%, grade III/IV in 20%, diarrhea grade I/II in 20%, leucopenia/thrombopenia grade I/II in 26. 7%, and grade III/IV in 13.3%. CONCLUSION Radiochemotherapy in locally advanced pancreatic cancer is an effective and well-tolerated treatment. The long-term efficacy concerning survival is limited. The integration of predictive factors and new chemotherapeutic agents like gemcitabine in the multimodality treatment may give a more promising perspective. Because of the narrow therapeutic index of gemcitabine-based radiochemotherapy schemes, a feasible combination of radiotherapy treatment volume and gemcitabine dose must be found.