The in vitro bacteriostatic activity of clarithromycin, a new macrolide derivative, against Rickettsia rickettsii, Rickettsia conorii, and "Rickettsia israeli" was determined by the plaque assay and the dye uptake assay. Both bacteriostatic and bactericidal activities of clarithromycin against the Nine Mile, Q212, Priscilla, and ME9 strains of Coxiella burnetti were evaluated by using three cell culture systems. Clarithromycin showed improved antibacterial activity compared with that of erythromycin. A bacteriostatic activity was obtained at concentrations below the reported maximum concentration of clarithromycin in human serum (about 4 micrograms/ml) for all tested rickettsiae. MICs ranged from 1 to 2 micrograms/ml for the three Rickettsia species and from 1 to 4 micrograms/ml for the C. burnetti strains. No bactericidal activity against C. burnetti was obtained when clarithromycin was used at 4 micrograms/ml.