To determine the metabolic responses to surgical trauma, we assessed the rates of whole body (WB) proteolysis and glucose turnover using established isotopic techniques in combination with interorgan amino acid and substrate balances (using arteriovenous differences times flow) after laparotomy. Circulating levels of hormones and mediators known to affect these parameters were also examined. Mongrel dogs (n = 5–8 per group) were studied postoperatively under general anesthesia (immediate postoperative period) and at 3 days postoperatively (3 dPO) and 2 weeks later. Our results show that the immediate postoperative period is characterized by significant hyperglycemia, secondary to decreased glucose clearance (without any alterations in the rates of hepatic glucose production) and significant increase in gut proteolysis, with a mild increase in WB proteolysis. The gut proteolysis accounted for nearly 40% of WB proteolysis. At 3 dPO, blood glucose levels returned to normal, whereas the rate of WB proteolysis was maximally increased. Gut proteolysis was mildly elevated and accounted for nearly 8% of WB proteolysis. All metabolic parameters were back to near basal at 2 weeks postoperatively. These metabolic changes were accompanied by significant elevations in the plasma levels of endogenous morphine and cortisol and lower glucagon and insulin growth factor-l levels in the immediate postoperative period and at 3 dPO. These studies underscore the importance of the gut as a reservoir of amino acids during the immediate postoperative period, accounting for more than one-third of WB proteolysis. At 3 dPO, when maximal stimulation of WB proteolysis and amino acid oxidation are observed, the contribution from the gut is negligible and is most likely replaced by breakdown from skeletal muscle.