Following massive small bowel resection, the remaining small bowel increases in mucosal weight, protein, deoxyribonucleic acid (DNA) content and absorptive function. Enteral nutrients are known to be important in stimulating this response. Recently, glutamine has been described as an essential fuel for the small intestinal mucosa and is thought to be trophic to the small bowel. We investigated if glutamine, when added to the diet in large quantities, might stimulate mucosal adaptation beyond that which normally occurs following physiologic feedings. Male Sprague-Dawley rats were placed on powdered rat chow supplemented with either 5% glutamine, 5% glycine or 5% glucose. After 4 days rats underwent 70% jejunoileal resection. Fourteen days after resection, protein, DNA and sucrase activity in the duodenum of the glutamine-fed animals were all significantly lower than results from both the glycine and glucose groups. Duodenal mucosal weight was lower in the glutamine group than in the glycine group. In the ileum, DNA content was significantly lower for the glutamine group than the glycine group. These results suggest that high concentrations of glutamine in the diet can have negative effects on intestinal adaptation.