In four patients undergoing reversal of jejunoileal bypass we compared functional (in continuity) with bypassed intestine in order to determined the effects of luminal contents. Total mucosal thickness, villus height, and crypt depth, as well as in vitro fatty acid esterification activity were determined. Morphological studies in segments exposed to luminal contents revealed that the ileum had a greater mucosal thickness than the jejunum (p less than 0.001) and that the difference was reflected in both villus height and crypt depth (p less than 0.001). The functioning segments of both jejunum and ileum had a greater mucosal thickness than corresponding bypassed segments consequent to a difference in villus height (p less than 0.001) but not crypt depth. Despite similar exposure to luminal contents, total fatty acid esterification was significantly higher (p less than 0.001) in the functioning jejunum than in the ileum. Jejunum incontinuity possessed higher esterification activity than bypassed jejunum. These results indicate that 1) luminal contents are the most important modulator of intestinal fatty acid esterification activity and the absence of luminal contents in bypassed intestine leads to a significant reduction in esterification activity, 2) the jejunum and ileum possess intrinsic differences in esterification activity even when both are exposed to an identical luminal environment.