The objective of this study was to determine the serum bactericidal activity (SBA) of levofloxacin against Streptococcus pneumoniae strains with various degrees of susceptibility to penicillin and cefotaxime. Serum samples of volunteers (n = 12) who had received levofloxacin 500 mg as a single po dose were provided in blinded fashion. SBA was determined, using the microdilution method, in Todd-Hewitt broth supplemented with lysed horse blood inoculated with an overnight culture diluted to yield a final concentration of approximately 10(5) cfu/mL. The serum bactericidal titre was defined as the highest dilution of serum showing no growth (> 99.9% reduction of inoculum). The duration of SBA ranged from 0.75 to 6.3 h (mean 3.85 h), and was independent of the susceptibility of the strains to penicillin and cefotaxime. In conclusion, a single po dose of 500 mg levofloxacin achieved serum concentrations which were bactericidal against penicillin-resistant S. pneumoniae for a mean period of 3.85 h.