This study was undertaken to examine the effect of feeding 2 defined-formula diets, Isocal and Portagen, on intestinal morphology and transport function in rabbits subjected to an ileal resection, and in control animals with an intact intestinal tract. Neither ileal resection nor feeding Isocal or Portagen significantly altered jejunal mucosal surface area. In animals with an intact intestinal tract, feeding Isocal was associated with decreased jejunal uptake of 2 mM glucose, whereas both Isocal and Portagen were associated with increased jejunal uptake of 40 mM glucose, and increased ileal uptake of 2 mM glucose, as compared with rabbits fed chow. In animals with an ileal resection, feeding Isocal was associated with increased jejunal and colonic uptake of galactose, whereas jejunal uptake of glucose was unaffected. Thus, (1) feeding defined-formula diets alters the intestinal active uptake of sugars without altering intestinal mucosal surface area; (2) sugar uptake rates were generally higher in animals fed Isocal than in those fed Portagen; (3) ileal resection obscured the differences in the jejunal uptake of higher concentrations of glucose observed in control rabbits (with an intact intestinal tract) fed these defined-formula diets; and (4) the differences in the effects of defined-formula diets on sugar uptake in control and resected animals was likely due to a direct effect on the glucose and galactose carrier(s), rather than to an indirect effect on food consumption, body weight gain, intestinal morphology, or the effective resistance of the intestinal unstirred water layer. It is suggested that the functional differences observed between animals fed Isocal versus Portagen may be due to the varying source of lipids and proteins in these diets, their different ratios of saturated-to-polyunsaturated fatty acids, and their different percent content of carbohydrate.