Fifty-one children with Mediterranean spotted fever (MSF) were randomized to receive either clarithromycin, 15 mg/kg/day orally in 2 divided doses, or chloramphenicol, 50 mg/kg/day orally in 4 divided doses, for 7 days. Mean time to defervescence was 36.7 h in the clarithromycin group and 47.1 h in the chloramphenicol group (P=.047). Clarithromycin could be an acceptable therapeutic alternative to chloramphenicol and to tetracyclines for children aged <8 years with MSF.