Resistance to first-line antimicrobial agents in Streptococcus pneumoniae is increasing worldwide and the new fluoroquinolones may provide a good alternative. The antimicrobial susceptibility to levofloxacin and 13 other antibiotics of 300 isolates of S. pneumoniae, isolated in the Madrid community in 1999 and 2000, was determined. A total of 65.6% of isolates were penicillin intermediate or resistant strains. A high percentage of resistance to macrolides, clindamycin, tetracycline and chloramphenicol was also observed, mainly in penicillin-resistant strains. All but one strain was susceptible to levofloxacin.