Technical Abstract: Tropical enteropathy is an asymptomatic villous atrophy of the small bowel that is prevalent in the developing world and is associated with altered intestinal function and integrity. The histology of tropical enteropathy resembles that seen in small-bowel bacterial overgrowth. This study tested the hypothesis that treatment of 3- to 5-y-old Malawian children with the probiotic Lactobacillus GG would improve their intestinal function and integrity. Clinically healthy children (n = 164) were enrolled in a placebo-controlled, randomized, double-blind trial. Intestinal function and integrity were measured by using the site-specific sugar-absorption test before and after 30 d of treatment with Lactobacillus GG or placebo. The primary outcomes were the ratios of urinary lactulose to mannitol (L:M) and of urinary sucrose to lactulose (S:L) excretion. Of the 161 children who completed the study, 119 (73%) had tropical enteropathy on enrollment (L:M > 0.10). Children receiving Lactobacillus GG did not differ significantly from the placebo group in the excretion (in % of dose administered) of mannitol (mean +/- SD: 8.9 +/- 4.4 and 8.9 +/- 3.9, respectively), lactulose (0.31 +/- 0.20 and 0.33 +/- 0.23, respectively), or sucrose (0.078 +/- 0.058 and 0.082 +/- 0.075, respectively). L:M and S:L also did not differ significantly between the Lactobacillus and placebo groups (0.19 +/- 0.13 and 0.20 +/- 0.12, respectively, for L:M; 0.58 +/- 0.46 and 0.65 +/- 0.57, respectively, for S:L). Administration of Lactobacillus GG for 30 d had no effect on the intestinal integrity of 3- to 5-y-old Malawian children.