The in-vitro and in-vivo susceptibility of Borrelia burgdorferito tetracycline, erythromycin and azithromycin was investigated. A macrodilution broth technique was used to determine MBCs. B. burgdorferi was most susceptible to azithromycin (MBC 0.04 mg/l) followed by erythromycin (MBC 0.16 mg/l) and tetracycline (MBC 1.6 mg/l). Syrian hamsters were used to determine ED50S for the three antimicrobials. Azithromycin was most effective in the elimination of spirochaetes from experimentally infected hamsters with an ED50 of 3.71 (+/- 1.9) mg/kg followed by tetracycline (ED50 15.6 (+/- 4.58) mg/kg). Erythromycin possessed low activity, having an ED50 of 122.2 (+/- 51.9) mg/kg. Tissue concentrations of azithromycin exceeding the MBC were present 24 h after the final treatment.