A nationwide multicenter susceptibility surveillance study (Susceptibility to the Antimicrobials Used in the Community in España [SAUCE] project), SAUCE-4, including 2,559 Streptococcus pneumoniae, 2,287 Streptococcus pyogenes, and 2,736 Haemophilus influenzae isolates was carried out from May 2006 to June 2007 in 34 Spanish hospitals. Then, the results from SAUCE-4 were compared to those from all three previous SAUCE studies carried out in 1996-1997, 1998-1999, and 2001-2002 to assess the temporal trends in resistance and the phenotypes of resistance over the 11-year period. In SAUCE-4, on the basis of the CLSI breakpoints, penicillin (parenteral, nonmeningitis breakpoint) and cefotaxime were the antimicrobials that were the most active against S. pneumoniae (99.8% and 99.6%, respectively). Only 0.9% of isolates had a penicillin MIC of > or = 2 microg/ml. In S. pyogenes, nonsusceptibility to erythromycin was observed in 19.4% of isolates. Among the H. influenzae isolates, a beta-lactamase-positive prevalence of 15.7% was found. A statistically significant temporal decreasing trend over the 11-year period was observed for nonsusceptibility (from 60.0% to 22.9%) and resistance (from 36.5% to 0.9%) to penicillin and for the proportion of erythromycin-resistant isolates of S. pneumoniae of the macrolide-lincosamide-streptogramin B (MLS(B)) phenotype (from 98.4% to 81.3%). A similar trend was observed for the prevalence of ampicillin resistance (from 37.6% to 16.1%), beta-lactamase production (from 25.7% to 15.7%), and beta-lactamase-negative ampicillin resistance (BLNAR) in H. influenzae (from 13.5% to 0.7%). Among erythromycin-resistant isolates of S. pyogenes, a significant increasing trend in the prevalence of MLS(B) was observed (from 7.0% to 35.5%). SAUCE-4 confirms a generalized decline in the resistance of the main respiratory pathogens to the antimicrobials as well as a shift in their resistance phenotypes.