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This study estimated the clinical effectiveness of five different antibiotic regimens (doxycycline, chloramphenicol, ciprofloxacin, doxycycline plus chloramphenicol, and doxycycline plus ciprofloxacin) administered for infection with Rickettsia typhi in terms of the duration of the fever. Eighty-seven patients with endemic typhus were hospitalized between 1993 and 1998 at the General Hospital of Chania in Chania, Crete, Greece. The mean time to defervescence was 2.9 days for doxycycline, 4.0 days for chloramphenicol, and 4.2 days for ciprofloxacin. In patients receiving combinations of doxycycline plus chloramphenicol and doxycycline plus ciprofloxacin, fever subsided in 3.4 and 4.0 days, respectively. The outcome was favorable in all patients, and no deaths or relapses were observed within two months.