Glutamine is an important fuel utilized by the intestinal mucosa that is not present in standard amino acid nutrition solutions. In order to determine the effects of glutamine on the intestine, glutamine enriched nutrition was administered intravenously to male Wistar rats. A standard amino acid solution was enriched with 1 and 2 g/100 ml of glutamine or glycine and used as part of a parenteral nutrition regime for 7 days. Intestinal samples were taken for measurements of jejunal weight, DNA, protein, mucosal thickness and villus height. Animals receiving 2 g glutamine/100 ml in the nutrition solution had increased intestinal weight, DNA, and villus height when compared to animals receiving 2 g/100 ml of glycine. No increase in the intestinal parameters was noted when 1 g/100 ml of glutamine was used. To investigate the dose-response effects of glutamine, further studies were performed using isonitrogenous and isocaloric solutions containing 0, 2, and 3 g of glutamine/100 ml. Animals receiving glutamine had a significant increase in mucosal weight, DNA, protein and villus height when compared to animals receiving no glutamine in the parenteral solutions. There was a dose-response relationship between the increase in jejunal DNA and the increased intake of glutamine (r = 0.93, p less than 0.01) but no correlation with the nitrogen content of the solutions (r = 0.18, p = 0.8). Total body nitrogen retention was greater in animals receiving 2 g/100 ml of glutamine (166 +/- 12 mg, days 6/7) when compared to those receiving 0 and 3 g of glutamine/100 ml (126 +/- 14 mg and 138 +/- 16 mg, respectively, p less than 0.05). These studies demonstrate that glutamine enriched nutrition protects against atrophy of the intestinal mucosa and when given at 2 g/100 ml improves nitrogen retention during intravenous feeding.