The efficacy and safety of fleroxacin in brief self-treatment of travelers' diarrhea were studied. In The Gambia, 195 tourists with acute diarrhea were randomized in a double-blind, controlled trial into three treatment groups: fleroxacin 400 mg for 1 day, fleroxacin 400 mg daily for 2 days, and placebo. Microbiology of stools was assessed only at recruitment. In the fleroxacin-treated groups, stool consistency was normal in 67% and 71% of the volunteers after 48 hours, as compared to 37% in the placebo group (p < 0.01). The time to total relief of diarrhea and of all symptoms was also significantly shorter in fleroxacin-treated patients. Adverse events, particularly slight neuropsychiatric reactions (headache, insomnia) were more frequent in the fleroxacin-treated groups (p < 0.05). There was no statistically significant difference in efficacy and tolerance if fleroxacin was administered for 1 or 2 days. A single dose of fleroxacin 400 mg may be recommended for the self-treatment of travelers' diarrhea.