BACKGROUND: During cancer, proteins are chronically wasted, including proteins of the gut. Surgical stress acutely increases protein breakdown of the gut. Surgery in cancer patients may thus have a double effect on the gut and lead to exhaustion and functional loss of the gut. METHODS: Female Lewis rats (+/-200 g) were studied bearing a subcutaneous tumor or after sham implantation. Hysterectomy was performed in half of the rats as a standardized operative procedure. Postoperative protein kinetics of the gut were determined using a primed constant infusion of L-[2,6-(3)H]-phenylalanine. Gut function was assessed by testing its permeability for sugar probes lactulose and L-rhamnose. Villus height and crypt depth were measured and polyamine concentrations were measured as markers for mucosal proliferation and differentiation. RESULTS: In control rats, gut protein breakdown increased from 6 +/- 3 to 32 +/- 8 nmol phenylalanine x 100 g body wt x min after hysterectomy. This was accompanied by increased amino acid membrane transport rates and metabolic shunting. In tumor-bearing rats, increased protein breakdown in response to surgery was attenuated (8 +/- 4 vs 17 +/- 4 nmol x 100 g body wt x min). Surgery increased the lactulose/L-rhamnose recovery ratio, indicating increased gut permeability. In the presence of a tumor gut permeability also increased and it increased further after surgery. No changes in villus height or polyamine levels could explain the increased permeability of the gut. CONCLUSION: The study shows that a mild surgical trauma increases protein breakdown of the gut and simultaneously increases gut permeability. In the presence of a tumor the metabolic response to surgery is attenuated. Gut barrier loss was highest in the combined presence of cancer and the surgical insult.