This study examined the relationship among time-dose-fractionation, development of intestinal complications, and histopathologic radiation injury in rat small bowel. In 177 rats, a functional loop of rat ileum was surgically transposed to the left scrotum. Three weeks later, fractionated irradiation was delivered to the transposed intestine as 2.8 Gy or 5.6 Gy daily fractions, or as 2.8 Gy twice daily with 12 hours' interval. Eleven experimental groups received total doses ranging from 28 Gy to 90 Gy. The animals were observed for intestinal complications, and groups of animals were killed 2 and 26 weeks after completion of irradiation for assessment of injury. Radiation injury was assessed by a semiquantitative histopathologic scoring system and by the frequency of lethal intestinal complications. Both increased fraction size and reduced overall treatment time increased the severity of subacute and chronic radiation injury, as well as frequency of intestinal complications. We conclude that rapidly proliferating cells (mucosal epithelium) play a pivotal role in the pathogenesis of radiation enteropathy and mechanisms other than radiation-induced mitotic cell death are pathogenetically involved.