It has been hypothesized that, following colectomy and endorectal ileal pullthrough with ileal reservoir (PTR), reservoir tissue might lose some of its normal nutrient transport capacity and assume properties of the colon. Whether reservoir size influences the expected alterations in normal mucosal absorption and thus contributes to changes in intraluminal ecology has not previously been investigated. To study this, the everted intestinal sleeve technique was used to measure uptake of four nutrients in two groups of dogs who underwent PTR: five with a small (5 cm) lateral reservoir and five with a large (18 cm) reservoir. Mucosal samples were taken from normal ileum and colon and from reservoirs 3 months postoperation. Active uptake of carbohydrates (glucose), amino acids (proline), and bile acids (taurocholate) and passive uptake of short chain fatty acids (propionate) were markedly decreased in mucosa of both reservoir sizes compared to normal ileum (P less than 0.05, t test) and more closely approximated that of normal colon. Uptake of glucose, proline, and taurocholate in large reservoirs was significantly less than that in small reservoirs (P less than 0.05). We conclude that (1) ileal reservoir mucosa has a significantly reduced capacity for nutrient uptake, (2) ileal mucosa in small reservoirs shows higher nutrient uptake rates than mucosa in large reservoirs, and (3) short, well-emptying reservoirs appear best suited to optimizing the intraluminal environment and thus enhance reservoir function when performing PTR.