OBJECTIVE: To compare glucose and rice-based oral rehydration solution with rice-based oral rehydration solution containing recombinant human lactoferrin and recombinant human lysozyme in diarrhea outcomes. PATIENTS AND METHODS: We conducted a randomized, double-blind controlled trial in children with acute diarrhea and dehydration. One hundred and forty children 5 to 33 months old were block randomized to receive low osmolarity WHO-ORS (G-ORS), rice-based ORS (R-ORS), or rice-based ORS plus lactoferrin and lysozyme (Lf/Lz-R-ORS). Intake and output were monitored for 48 h in the ORU, with continued monitoring through home and clinic follow-up for 14 d. RESULTS: The G-ORS and R-ORS groups did not show any differences in diarrhea outcomes and were therefore combined as the control group. Intent-to-treat analysis showed a significant decrease in duration of diarrhea (3.67 d vs 5.21 d, P = 0.05) in the Lf/Lz-R-ORS group as compared with the control group and a significant increase in the number of children who achieved 48 h with solid stool, 85% vs 69% (P < 0.05). There were also decreases in volume of diarrhea and the percentage of children who had a new diarrhea episode after achieving the endpoint. CONCLUSIONS: Addition of recombinant human lactoferrin and lysozyme to a rice-based oral rehydration solution had beneficial effects on children with acute diarrhea. © 2007 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.