To examine whether the intestinal mucosa in uremia is more prone to injury, we studied acute intestinal mucosal injury in rats with experimental chronic renal failure (RF) and sham-operated and starved control animals. Intestinal injury was produced by perfusing intestinal segments in vivo with 5 mmol/L chenodeoxycholic acid. Histologic specimens were then taken from the proximal and distal perfused and unperfused intestinal segments. Quantitative morphometry was done with computerized image analysis, and samples of the unperfused intestine were assayed for protein and DNA content. Chronic RF did not significantly affect the functional or morphologic injury caused by chenodeoxycholic acid. However, it was noted that RF rats had consistently taller villi and deeper crypts in all the samples studied. The protein content and the ratio of DNA to protein was similar among the three groups. The mechanism of the increase in villus height and crypt depth in the RF rats was not related to increases in tissue water content or to alterations in protein or DNA content, and the mechanism thus remains unexplained. This study clearly demonstrates, however, that the intestinal mucosa of rats with chronic renal insufficiency is not more susceptible to mucosal injury by bile acids than is the mucosa of appropriate control animals.