A double-blind, randomized, placebo-controlled trial was conducted to evaluate the efficacy and safety of fleroxacin for one or two days as treatment for patients with travellers' diarrhoea. A total of 195 patients who were suffering with acute diarrhoea of less than six days' duration were enrolled. One hundred and fifty-one patients, of whom 49 received placebo, 54 received fleroxacin 400 mg for one day and 48 received fleroxacin 400 mg for two days, were included in the analysis of efficacy. The results showed that fleroxacin was significantly superior to placebo, but that there was no significant difference in terms of efficacy between the one- and two-day regimens. Adverse events, particularly minor neuropsychiatric disturbances such as headache and insomnia, were significantly more common amongst patients receiving active treatment. In conclusion, a single dose of fleroxacin 400 mg could be recommended as self-treatment for visitors to high-risk countries who develop travellers' diarrhoea.