This study compared fleroxacin, 400 mg daily for 7 or 14 days, with chloramphenicol, 50 mg/kg per day for 14 days, for the treatment of patients with typhoid fever in a multicenter study. A total of 184 patients were randomly assigned to the three treatment groups. Efficacy was determined by culture of blood and stool, overall clinical response, and time to defervescence. Safety was assessed by occurrence of adverse events and laboratory abnormalities. A total of 97 patients were evaluable for efficacy, 28 in the fleroxacin 7-day group, 35 in the fleroxacin 14-day group, and 34 in the chloramphenicol group. All showed rapid defervescence with high cure rates. Bacteriologic cure rates were 96% in the fleroxacin 7-day group, 97% in the fleroxacin 14-day group, and 85% in the chloramphenicol group. Clinical cure rates were 83-100% with fleroxacin and 82% with chloramphenicol. The time to defervescence was shorter for patients treated with fleroxacin than for those treated with chloramphenicol. All three treatment regimens were well tolerated. Fleroxacin, 400 mg daily for 7 days, appears to be satisfactory for the treatment of typhoid fever and compares favorably with the standard 14-day therapy with chloramphenicol.