Background: Increases in penicillin-resistant Streptococcus pneumoniae have been documented worldwide. Methods: During 1999 and 2000, 5,015 S. pneumoniae isolates were collected from 13 countries on five continents and tested for antimicrobial susceptibility. Results: Penicillin resistance rates were as follows: South Korea, 70.1%; Hong Kong, 50.3%; Thailand, 39.3%; France, 28.7%; Spain, 24.8%; Mexico, 18.1%; Ireland, 11.8%; South Africa, 11.1%; Italy, 9.4%; United Kingdom, 3.1%; Brazil, 2.9%; China, 2.3%, and Germany, 0.7%. Resistance to azithromycin, clarithromycin and trimethoprimsulfamethoxazole was commonly associated with penicillin resistance. Levofloxacin-resistant isolates were detected in 8 of 13 countries: Germany (0.2%), France (0.4%), Thailand (0.5%), South Korea (0.9%), Mexico (1.5%), Spain (1.6%), China (3.3%) and Hong Kong (8.0%). Multidrug resistance (resistance to greater than or equal to3 antimicrobial classes) occurred in 626/5,015 isolates (12.5%). Levofloxacin was active against 96.0% (601/626) of the multidrug-resistant (MDR) isolates and 99.7% (4,374/4,389) of the non-MDR isolates. Conclusion: Although relatively high levels of levofloxacin resistance were detected in China and Hong Kong, overall, levofloxacin remained active against >99% of clinical isolates of S. pneumoniae despite their resistance to other agents. Continued surveillance of S. pneumoniae will track any changes in levofloxacin activity, should they occur. Copyright (C) 2002 S. Karger AG, Basel.