This study was performed to determine whether the addition of alanyl-glutamine (Ala-Gln) can prevent intestinal mucosal atrophy induced by standard solution of total parenteral nutrition (S-TPN). Forty-one male Sprague-Dawley rats weighing 250 g were randomly divided into four groups: group I was killed after overnight fasting; group II received S-TPN. The other groups received S-TPN supplemented with amino acids other than glutamine (group III) or supplemented with Ala-Gln 2 g/100 mL (group IV); both solutions were isocaloric and isonitrogenous. After 1 week of TPN the rats were killed, and the duodenum, proximal jejunum, mid-small bowel, and distal ileum were obtained for morphologic and functional analysis. Weight gain did not differ significantly among these four groups, and there was no difference in nitrogen balance between groups III and IV. Serum glutamine in group IV (102.8 +/- 13.3 mumol/dL) was significantly increased (p less than .05) compared with groups I, II, and III (66.2 +/- 3.9, 55.7 +/- 7.8, and 61.3 +/- 10.8 mumol/dL, respectively). Mucosal wet weight, protein, RNA, sucrase, and maltase of group IV were significantly increased (p less than .05) compared with groups II and III. Villus height was significantly increased (p less than .05) in the jejunum of group IV rats compared with groups II and III, but not in any other segments of the intestine. No significant changes were observed in crypt depth among all groups. Diamine oxidase in groups II, III, and IV was significantly decreased (p less than .05) compared with group I in all segments except for the ileum.(ABSTRACT TRUNCATED AT 250 WORDS)