Following small intestinal transplantation for the short-bowel syndrome the absorptive capacity of the grafted bowel is markedly reduced in the early postoperative period. This impairment is thought to be due primarily to perioperative ischemic damage and complete denervation. To determine which of these was the more important factor, we compared three groups of mongrel dogs. A sham-operated group (n = 5), a denervation group (n = 4), and an autotransplantation group (n = 5). D-xylose absorption and graft tissue levels of substance P and ATP were measured at 4 and 5 weeks postoperatively. A significant reduction in the intestinal absorption of D-xylose was observed in the denervation and autotransplantation groups (P < 0.01, P < 0.05). In contrast, the denervation and autotransplantation groups had significantly higher substance P levels in small-bowel biopsy tissues than the control group (P < 0.01). However, the tissue ATP levels were similar in all three groups, suggesting that perioperative ischemic damage was reversible. These findings indicate that the impaired absorption following small-bowel autotransplantation was largely due to intestinal denervation.