Erythromycin therapy was compared with no treatment in a prospective trial of acute diarrheal disease among 100 infants in an orphanage in Bangkok. Within 24 h of the onset of diarrhea, 50 children received erythromycin ethylsuccinate (40 mg/kg per day) in four divided doses for 5 days. Campylobacter jejuni isolated from 31, Campylobacter coli isolated from 21, and Shigella spp. isolated from 21 of 100 children were the most commonly recognized pathogens; use of a sensitive, nonselective method substantially increased Campylobacter isolation. Treatment with erythromycin had no effect on the duration of diarrhea caused by Campylobacter spp., Shigella spp., or other agents; 37% of the treatment group and 35% of the control group had diarrhea for 1 week. Of 23 Campylobacter strains isolated from the treatment group before treatment, 15 (65%) were resistant (MIC, greater than or equal to 8 micrograms/ml) to erythromycin. Among orphanage-acquired strains, 53% of 43 C. jejuni strains and 91% of 23 C. coli strains were resistant to erythromycin compared with 11% of 114 C. jejuni strains and 46% of 35 C. coli strains that were community acquired. Erythromycin resistance is common among Campylobacter strains in Bangkok, especially in an institutional setting, which may account for the lack of efficacy of erythromycin for treatment of acute diarrheal illnesses.