Due to paucity of suitable animal models, it has been difficult to study the development of long-term intestinal complications following fractionated irradiation. We recently developed a model which allows multiple radiation exposures of a short segment of rat ileum without the need for repeated surgery. In the present series, this model was used to study the influence of shortening the total treatment time (accelerated fractionation) on development of radiation enteropathy. Male rats were orchiectomized and a short segment of distal ileum was transposed to the scrotum. Starting 3 weeks after surgery, the scrotum containing the intestinal segment was x-irradiated with 20 fractions of 2.8 Gy (total dose 56 Gy). Two fractionation schedules were compared: One fraction per day (total treatment time 26 days) and 3 fractions per day (total treatment time 7 days). Actuarial survival curves were obtained, and the degree of radiation injury was assessed 2, 8, and 26 weeks after the last radiation exposure using a semiquantitative histopathologic scoring system. There was no mortality from acute radiation injury in either treatment group. All animals of the 1-fraction/day group survived the observation period (26 weeks). In the 3-fraction/day group, there was significant mortality due to intestinal obstruction, and cumulative mortality at 26 weeks was 100%. Radiation injury, as assessed by the histopathologic scoring system, was also more pronounced in this group than in the 1-fraction/day group. We conclude that shortening the total treatment time significantly increases the severity of late intestinal complications. Our data are suggestive of an association between acute mucosal damage and chronic radiation injury of the small intestine.