We conducted a randomized controlled trial to determine whether empirical treatment of severe acute community-acquired gastroenteritis (four fluid stools per day for > 3 days) with ciprofloxacin reduces the duration of diarrhea and other symptoms and to determine what effect ciprofloxacin has on the duration of long-term fecal carriage of gastrointestinal pathogens. A total of 173 patients were recruited for the study and received either ciprofloxacin (500 mg b.i.d.) or placebo for 5 days, during which time they recorded the duration of diarrhea and other symptoms (fever, abdominal pain, vomiting, and myalgia). Fecal samples were collected before treatment and regularly after treatment to determine the duration of carriage of gastrointestinal pathogens. Antibiotic susceptibility tests were performed, and the minimum inhibitory concentrations (MICs) of ciprofloxacin were determined. A significant reduction in the duration of diarrhea and other symptoms was observed after treatment, regardless of whether a pathogen was detected (P = .0001). Treatment failure occurred in 3 of 81 patients in the ciprofloxacin group and 17 of 81 patients in the placebo group. Significant pathogens were detected in 87% of patients, 85.5% of whom had cleared the pathogen at the end of treatment with ciprofloxacin, as compared with 34% who received placebo. Six weeks after treatment, there was no difference between the two groups in terms of the pathogen carriage rate (12%). Treatment with ciprofloxacin did not prolong carriage. High-level resistance to ciprofloxacin (MIC, > 32 mg/L) was detected in three strains (4%) of Campylobacter species.