Certain strains of lactobacilli may promote recovery from acute diarrhea. Lactobacillus reuteri is of human origin and is a natural colonizer of gastrointestinal tract. In this trial, exogenously administered L. reuteri was studied as a therapeutic agent in acute diarrhea. Forty patients between 6 and 36 months of age hospitalized with acute diarrhea (75% rotavirus) were studied. After parental consent, the patients were randomized to one of two treatment groups to receive either 10(10) to 10(11) colony-forming units of L. reuteri or a matching placebo daily for the length of hospitalization or up to 5 days. The clinical outcome of diarrhea and colonization of L. reuteri were evaluated. The mean (SD) duration of watery diarrhea after treatment was 1.7 (1.6) days in the L. reuteri group and 2.9 (2.3) days in the placebo group (p = 0.07). On the second day of treatment only 26% of patients receiving L. reuteri had watery diarrhea, compared with 81% of those receiving placebo (p = 0.0005). Cultures of lactobacilli from stool samples demonstrated that administration of L. reuteri resulted in colonization of the gastrointestinal tract. Lactobacillus reuteri accounted for > 75% of the total lactobacilli found in children fed with this product. Lactobacillus reuteri is effective as a therapeutic agent in acute rotavirus diarrhea in children. Further studies are warranted to confirm the present finding and to explore the full therapeutic potential of L. reuteri in acute viral diarrhea.