The study presented here determined the relationship between antimicrobial resistance in Streptococcus pneumoniae and the use of antimicrobial agents in 15 different European countries. Pneumococcal isolates (n = 1974) recovered from patients with community-acquired respiratory tract infections during the winter of 2004-2005 in 15 European countries were characterized. The overall percentages of isolates demonstrating intermediate or complete resistance to penicillin, erythromycin, tetracycline, trimethoprim-sulfamethoxazole (TMP-SMX) and ciprofloxacin were 24, 24.6, 19.8, 26.7 and 2%, respectively, as determined using the broth microdilution MIC method recommended by the Clinical and Laboratory Standards Institute. The overall and mean antimicrobial consumption levels (ACL)--i.e., the defined daily doses per 1,000 inhabitants per day--were obtained from the European Surveillance of Antimicrobial Consumption project for each of the 15 countries for the years 1998-2004. Using linear regression analysis, the mean annual ACL for beta-lactams, macrolides, tetracyclines, TMP-SMX and fluoroquinolones in each country was compared to the country-specific resistance rates determined in 2004-2005. The rate of overall antimicrobial use in all 15 European countries was significantly associated with antimicrobial resistance in S. pneumoniae. There was variation among the different antimicrobial classes as drivers of resistance, with beta-lactams having the strongest association.