To study the influence of luminal nutrition on the structural and functional adaptive changes which are seen in the residual intestine after partial small bowel resection, quantitative histology, in vitro uptake of 14C l-leucine, mucosal enzyme activities, and in vivo absorption of glucose were studied before and 6 weeks after 50% proximal small bowel resection in 10 greyhound dogs, 5 of which were nourished exclusively by the intravenous route while 5 were pair-fed by mouth. In the orally fed jejunectomized dogs, the ileum became dialed with mucosal hyperplasia, the villus height increased from 796 +/- SEM 26 mum to 1102 +/- 28 mum (P less than 0.001), and there was a corresponding increase in glucose absorption in vivo (milligrams -centimeter of intestine -1min-1) from 5.3 +/- 1.2 to 10.1 +/-1.6. The increased absorption seems mainly caused by the dilation and villus hyperplasia, since there was no significant change in in vitro absorption and mucosal enzyme activity when expressed per unit weight of intestine. In the absence of exogenous luminal nutrition, the well nourished intravenously fed dogs showed no evidence of functional adaptation and a significant fall in mean ileal villus height from 823 +/-48 mum at the initial operation to 732 +/-57 mum 6 weeks after jejunectomy. These results provide the most direct evidence to date that luminal nutrition is essential for the development of intestinal adaptation after resection. They also suggest that luminal contents are necessary to maintain the structural and functional integrity of the normal small bowel.