A multi-center surveillance study was conducted in Thailand during 1999-2000 to determine antimicrobial susceptibilities among the respiratory pathogens Streptococcus pneumoniae (n = 206), Haemophilus influenzae (n = 305), and Moraxella catarrhalis (n = 39). Of the S. pneumoniae isolates collected, 33.5% were penicillin-susceptible, 27.2% intermediate and 39.3% resistant. Expectedly, resistance rates to beta-lactams were higher among penicillin-resistant (ceftriaxone, 14.8%; amoxicillin-clavulanate, 42.0%; cefuroxime, 100%) than penicillin-susceptible (ceftriaxone, 0%; amoxicillin-clavulanate, 0%; cefuroxime, 0%) isolates. Likewise, azithromycin and clarithromycin resistances were 4.3% and 5.8% among penicillin-susceptible isolates, and 77.8% and 95.1% among penicillin-resistant isolates. All S. pneumoniae remained susceptible to vancomycin and 99.5% were susceptible to levofloxacin. Multidrug resistance (resistance to >3 antimicrobial classes) was present in 25.2% of pneumococcal isolates (n = 52), with resistance to azithromycin, penicillin and trimethoprim-sulfamethoxazole the most common phenotype (40/52 isolates; 77.0%). Among the isolates of H. influenzae, the prevalence of beta-lactamase production was 45.2%. All isolates of H. influenzae were susceptible to amoxicillin-clavulanate, azithromycin, ceftriaxone, cefuroxime and levofloxacin while 49.5% were resistant to trimethoprim-sulfamethoxazole. All 39 isolates of M. catarrhalis produced beta-lactamase. Azithromycin (MIC90, < or = 0.03 microg/ml) and levofloxacin (MIC90, 0.03 microg/ml) were the most active agents tested against M. catarrhalis. The results of this study may serve as a baseline for future studies to monitor antimicrobial susceptibilities among respiratory pathogens in Thailand.