The aim of this study was to evaluate the relative potential of levofloxacin to select for resistance in Streptococcus pneumoniae in comparison with ciprofloxacin, sparfloxacin and ofloxacin. Two S. pneumoniae strains were studied; HBD 153 (parental strain, serotype 3) and HBD 964 (selected from the parental strain in an experimental mouse peritonitis infection model). MICs for the two strains were, respectively: 2 and 2 mg/L for ciprofloxacin; 2 and 4 mg/L for ofloxacin; 0.5 and 1 mg/L for sparfloxacin; 2 and 2 mg/L for levofloxacin. In-vitro, with 4 x MIC as the selection concentration, no mutant was obtained with strain HBD 153 (mutation frequency < 10(-8). With HBD 964, the mutation frequency was 9 x 10(-7) for ofloxacin, 10(-7) for ciprofloxacin, 4 x 10(-5) for sparfloxacin and < 10(-8) for levofloxacin. In an immunosuppressed mouse peritonitis model (20 mice per dose), the S. pneumoniae strains were studied with sc doses of ciprofloxacin, sparfloxacin and ofloxacin at 50 mg/kg od, and with sc levofloxacin at a dose of 10 and 50 mg/kg od, or 10 and 50 mg/kg bid. The MICs for strains isolated after antibiotic treatment and the mutation frequencies at 4 x MIC were determined. Against HBD 153, sparfloxacin was the most active treatment, followed by levofloxacin 10 mg/kg and 50 mg/kg bid, but strains identical to HBD 964 (showing a resistant variant at 4 x MIC) were selected by sparfloxacin. Against HBD 964, levofloxacin (10 mg/kg and 50 mg/kg) was the most active drug. Highly resistant mutants were selected by ofloxacin and ciprofloxacin, but not by sparfloxacin and levofloxacin. In conclusion, the relative potential of levofloxacin to select for fluoroquinolone-resistant S. pneumoniae is lower than that of ciprofloxacin, ofloxacin and sparfloxacin both in vitro and in vivo.