Non-resectable pancreatic adenocarcinomas (PA) are of poor prognosis with median survival of 4-6 months. Radiotherapy (RT) and chemotherapy (CT) association are potential palliative treatments recently investigated. We have tested such an association in a pilot study. Twelve patients (pts) with non-resectable PA and localized tumors were treated by 2 cycles of CT (5-FU + adriamycin + cisplatinum) and then 2 or 3 split courses of RT (20 Gy/12 days and 8 fractions with a 16 day interval). CT was reintroduced, if initially active, for 3 cycles. Results were: 3 CR (11+, 13+, 16 months) for a response rate of 25%, 1 MR (4 months) and 5 stabilizations longer than 6 months. The 1 year survival was 56 +/- 15% with no patient surviving longer than 2 years. Tolerance was acceptable for RT and toxicity with CT was digestive (grade II) for all pts, leucopenia grade III for 3 pts and thrombopenia grade II for 2 pts. Two pts experienced digestive hemorrhage for anastomatic ulceration, responsible for death in one case. This pilot study confirms the transient efficacy of RT + CT association for non-resectable PA. However, the toxicity and treatment duration lead us to recommend other studies of less toxic association before initiation of randomized trials.