We determined the in vitro susceptibilities of eight Borrelia burgdorferi isolates to five oral cephalosporins. MICs for B. burgdorferi 297 were 23-mu-g/ml (cephalexin), 45-mu-g/ml (cefadroxil), 91-mu-g/ml (cefaclor), 0.13-mu-g/ml (cefuroxime), 0.8-mu-g/ml (cefixime), and 0.02-mu-g/ml (ceftriaxone). When B. burgdorferi isolates were exposed to concentrations twice the MIC of cefuroxime, cefixime, or ceftriaxone, at least 72 h of incubation was required to kill 99% of the organisms.