The in vitro susceptibility of Borrelia burgdorferi to 11 antimicrobial agents was investigated. The antimicrobial agents evaluated included ceftizoxime, FK037, cefotaxime, dirithromycin, clarithromycin and its metabolite 14-hydroxy-clarithromycin, erythromycin, doxycycline, amoxicillin, ciprofloxacin, and ofloxacin. Isolates of B. burgdorferi tested included two reference strains (B31 and ATCC 53899), six isolates from the midwestern United States, and three from Europe. A broth macrodilution method was used to determine MICs and MBCs. B. burgdorferi was inhibited by < or = 0.5 micrograms of each of the agents except the quinolones per ml. The MBCs for 90% of strains tested of ceftizoxime, FK037, clarithromycin, 14-OH clarithromycin, and dirithromycin (< or = 1.0 microgram of each per ml) were superior to those of amoxicillin (2.0 micrograms/ml) and doxycycline (4.0 micrograms/ml). Further in vivo studies are warranted to determine whether these agents may be efficacious in the treatment of Lyme borreliosis.