Glutamine, an important fuel and biosynthetic precursor in intestinal epithelial cells, helps maintain intestinal integrity and function when supplemented to the diet of many species. The hypothesis tested here was that glutamine supplementation would overcome the decreased average daily gain (ADG) and altered intestinal morphology caused by milk replacer containing soy protein concentrate (SPC). Holstein calves (9 male and 1 freemartin female per treatment) were assigned to diets of 1) all-milk-protein (from whey proteins) milk replacer, 2) milk replacer with 60% milk protein replacement from SPC, and 3) SPC milk replacer as in diet 2 plus 1% (dry basis) l-glutamine. Milk replacers were reconstituted to 12.5% solids and were fed at 10% of body weight from d 3 to 10 of age, and at 12% of body weight (adjusted weekly) from d 10 through 4 wk of age. No dry feed (starter) was fed, but water was freely available. Glutamine was added at each feeding to reconstituted milk replacer. Five calves from each treatment were slaughtered at the end of wk 4 for measurements of intestinal morphology. The ADG was greater for calves fed the all-milk control than for those fed SPC; glutamine did not improve ADG (0.344, 0.281, and 0.282 kg/d for diets 1 to 3, respectively). Intake of protein was adequate for all groups and did not explain the lower growth for calves fed SPC. Villus height and crypt depth did not differ among treatments in the duodenum. In the jejunum, villus height (713, 506, and 464 mum, for diets 1 to 3, respectively) and crypt depth (300, 209, and 229 mum, respectively) were greater for calves fed all milk protein than for either SPC group. In the ileum, villus height was greater for calves fed all milk than for either soy group (532, 458, and 456 mum), whereas crypt depth tended to be greater (352, 301, and 383 mum for diets 1 to 3, respectively), and the villus to crypt ratio was lower for calves supplemented with glutamine than for those fed SPC alone. Urea N concentration in plasma was greater for calves supplemented with glutamine than for those fed SPC alone, indicating that glutamine was at least partially catabolized. Supplemental l-glutamine did not improve growth or intestinal morphology of calves fed milk replacer containing SPC.