We evaluated two doses of loperamide oxide (1 mg and 2 mg) and placebo in the treatment of acute diarrhea in 230 adult patients. Two tablets were taken initially and then one tablet after each watery, loose, or pasty stool to a maximum of eight tablets per day. The median time to complete relief was 27 hours 55 minutes for the 1-mg loperamide oxide group, 25 hours for the 2-mg loperamide oxide group, and 40 hours 35 minutes for the placebo group (P < 0.05). The investigator rated treatment as good or excellent for 78% of patients in each group treated with loperamide oxide and 62% of patients who received placebo. Constipation-like periods were no more common with loperamide oxide than with placebo. Adverse events were reported by four patients given loperamide oxide and three patients given placebo. The results demonstrate superior efficacy of loperamide oxide compared with placebo in the treatment of acute diarrhea in adults; because both doses of loperamide oxide are equally effective, the lower (1-mg) dose is preferred.