A nationwide multicenter susceptibility surveillance study which included 1,684 Streptococcus pneumoniae and 2,039 S. pyogenes isolates was carried out over 1 year in order to assess the current resistance patterns for the two most important gram-positive microorganisms responsible for community-acquired infections in Spain. Susceptibility testing was done by a broth microdilution method according to National Committee for Clinical Laboratory Standards M100-S10 interpretative criteria. For S. pneumoniae, the prevalences of highly resistant strains were 5% for amoxicillin and amoxicillin-clavulanic acid; 7% for cefotaxime; 22% for penicillin; 31% for cefuroxime; 35% for erythromycin, clarithromycin, and azithromycin; and 42% for cefaclor. For S. pyogenes, the prevalence of erythromycin resistance was 20%. Efflux was encountered in 90% of S. pyogenes and 5% of S. pneumoniae isolates that exhibited erythromycin resistance. Erythromycin resistance was associated with clarithromycin and azithromycin in both species, regardless of phenotype. Despite the different nature of the mechanisms of resistance, a positive correlation (r = 0.612) between the two species in the prevalence of erythromycin resistance was found in site-by-site comparisons, suggesting some kind of link with antibiotic consumption. Regarding ciprofloxacin, the MIC was >or=4 microg/ml for 7% of S. pneumoniae and 3.5% of S. pyogenes isolates. Ciprofloxacin resistance (MIC, >or=4 microg/ml) was significantly (P < 0.05) associated with macrolide resistance in both S. pyogenes and S. pneumoniae and with penicillin nonsusceptibility in S. pneumoniae.