BACKGROUND: Although tetracycline or doxycycline is the drug of choice for the treatment of scrub typhus, they are not recommended for children and pregnant women. Futhermore, the emergence of doxycycline resistant strain of Orientia tustusgamushi has aroused to find new therapeutic drugs. So, this study was aimed to evaluate the clinical efficacy of telithromycin, the first ketolide antibiotic for the treatment of scrub typhus in comparison with doxycycline. MATERIALS AND METHODS: Mild scrub typhus patients who were admitted to two university hospitals located in Incheon city from October 2004 through November 2004 were enrolled. Patients were assigned to telithromcyin (the first day, oral 800 mg every 12 hours and then 800 mg/day) and doxycycline treatment groups (oral 200 mg/day). Time and days to defevescence were analysed to evaluate the efficacy of the two antibiotics. RESULTS: Among a total of fifty patients, twenty six (52.0%) patients were excluded. Twenty four (48.0%) enrolled patients, telithromcyin and doxycycline were administered to thirteen (54.2%) and eleven patients (45.8%), respectively. In telithromycin treatment group, one patient (7.6%) was dropped out due to nausea and diarrhea. In doxycycline group, the mean age was higher (P=0.031) but the duration of fever before admission was shorter (P=0.015) than telithromycin group. There was no treatment failure nor relapse in either treatment groups. The mean time to defevescence was 17.7 hours for telithromycin group and 30.7 hours for doxycycline group (P=0.003). Ten patients (83.3%) in telithromycin group and four patients (36.4%) in doxycycline group became afebrile within the first day (P=0.048). CONCLUSION: Telithromycin has achieved good therapeutic outcome and more rapid response than doxycycline for the treatment of mild to moderate scrup typhus, so it suggests that telithromycin would be an alternative therapeutic agent for scrub typhus.