Two drugs, iodoxychloroquinoline (Mexaform®) and metronidazole (Flagyl®), were tested to determine their prophylactic effect against enteropathogenic bacteria and protozoa. These drugs and a suitable placebo were given in a rotatory fashion during four 16-week study periods to three equal groups of children, taken randomly and matched only by age. The results of the study demonstrated protective activity of the drugs. Iodoxychloro-quinoline diminished the prevalence of diarrhea and the rates of infection with Shigella and enteropathogenic Escherichia coli. Metronidazole was less effective in controlling diarrheal disease but showed a similar effect upon infections with Shigella and enteropathogenic strains of E. coli. Absence of Giardia lamblia from stools, effected by the prophylactic treatment with metronidazole, did not diminish the rate of diarrhea significantly. Moreover, there was no difference in prevalence of diarrhea in children infected with G. lamblia and those not infected. We conclude that chemoprophylaxis of diarrhea of bacterial or protozoan origin is feasible. The remaining infectious diarrheas, probably of viral origin, are not preventable with chemotherapy.