The PROTEKT surveillance study commenced in 1999 to examine the antimicrobial susceptibility of community-acquired respiratory pathogens. We report here the results from 2371 isolates collected during 2000 by North American centers (Canada, n = 7; USA, n = 8). Overall, 21.3% of pneumococci (n = 687) were penicillin G-resistant (Canada, 10.3%; USA, 32.6%). Corresponding rates of erythromycin resistance were 16.3% and 31.5%. Telithromycin inhibited all penicillin- and erythromycin-resistant isolates at ≤1 μg/ml. Among 612 Hemophilus influenzae isolates, 22.4% were β-lactamase-positive. Antimicrobial susceptibility of H. influenzae varied between 82.4% (clarithromycin) and 100% (cefpodoxime, levofloxacin). Importantly, one isolate was found to be resistant to both moxifloxacin and ciprofloxacin. Most Moraxella catarrhalis isolates were highly susceptible to the antimicrobials tested, except ampicillin. All Streptococcus pyogenes isolates (n = 382) were penicillin-susceptible and 5.2% were non-susceptible to erythromycin. S. pyogenes showed cross-resistance to other macrolides yet remained inhibited by telithromycin at ≤0.5 μg/ml. Methicillin resistance among Staphylococcus aureus was common (19.9%), particularly in the USA. The PROTEKT study confirms the widespread prevalence of antimicrobial resistance among common respiratory pathogens in North America, and hence the need for continued surveillance to guide optimal empiric therapy for community-acquired respiratory tract infections. © 2003 Elsevier Science Inc. All rights reserved.