Grepafloxacin and trovafloxacin are two novel fluoroquinolones with extended Gram-positive bacterial spectra compared with older quinolones. The aim of the present study was to investigate the different pharmacodynamic parameters of grepafloxacin in comparison with those of trovafloxacin. The following studies were performed against various Gram-positive and Gram-negative bacteria: (i) determination of the rate and extent of killing at a concentration corresponding to the 1 h non-protein-bound human serum level following an oral dose of 800 mg grepafloxacin and 300 mg trovafloxacin; (ii) determination of the rate and extent of killing of the two quinolones at different concentrations; (iii) determination of the post-antibiotic effects (PAEs); (iv) determination of the post-antibiotic sub-MIC effects (PA SMEs); (iv) determination of the rate and extent of killing in an in vitro kinetic model. It was shown that both grepafloxacin and trovafloxacin exhibited concentration-dependent killing against both Gram-positive and Gram-negative bacteria. Grepafloxacin exhibited a slower bactericidal effect against all the Gram-positive strains investigated in comparison with trovafloxacin in spite of a similar C(max)/MIC in the static experiments and a similar AUC/MIC ratio in the kinetic experiments. No major differences in the extent and rate of killing were noted against the Gram-negative strains, which were killed almost completely after 3 h except for Pseudomonas aeruginosa. A PAE of both quinolones was noted for all strains investigated. Trovafloxacin induced longer PAEs against the Gram-positive strains but shorter PAEs in comparison with those of grepafloxacin against the Gram-negative strains. A prolonging of the PAEs was noted for all bacteria when exposed to sub-MICs in the post-antibiotic phase. With a similar AUC/MIC of 310 for the penicillin-sensitive strain of Streptococcus pneumoniae and 143 for the penicillin-resistant strain, the time for 99.9% eradication for both strains was 2 h for trovafloxacin and 6 h for grepafloxacin.