The role of antibiotics in treating endemic infantile diarrhea caused by enteropathogenic Escherichia coli has not been determined. In a controlled study of 49 patients, one group received mecillinam and another group received trimethoprim-sulfamethoxazole. A third group served as control subjects. Serotype 0111:B4 dominated. Treatment, as evaluated clinically on the third day, resulted in cure for 790/0 of those receiving mecillinam, 73% of those receiving trimethoprim-sulfamethoxazole, and 7% of the control subjects. Bacteriologic cure was confirmed in 53%, 53%, and 0, respectively. The statistically significant difference between antibiotic-treated patients and control subjects (P < 0.001) indicated that antibiotics are an important supplement in the treatment of endemic severe diarrhea caused by enteropathogenic E. coli.