The Respiratory Surveillance Program (RESP) is a large-scale surveillance study of potential bacterial pathogens from respiratory tract infections that was performed over a 10-month period (July to April) during the 1999–2000 respiratory infection season. It is also the first study of its kind to derive its information entirely from community-based medical practices. This study, therefore, provides insight into the identity, frequency, and susceptibility of the possible pathogens isolated from patients encountered by primary care physicians. Reduction of antibiotic susceptibility in various bacterial pathogens may be of academic interest. However, it is only the emergence of clinical resistance (strains exhibiting minimum inhibitory concentrations above the resistance breakpoint) to commonly used antibacterial agents in the most prevalent species that has significant impact on empiric therapy choices. A review of data from RESP indicated that the most prevalent species were Moraxella catarrhalis, Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae. As expected, the prevalence of these bacterial isolates varied by disease state. The prevalence of clinical resistance to various antibiotics ranged, within these 4 species, between 0% and 92%. Resistance to the greatest number of drugs was expressed by S pneumoniae, followed by S aureus, H influenzae, and M catarrhalis. The prevalence of antibiotic resistance found among these community-isolated pathogens was surprisingly similar to that reported in hospital-based studies, suggesting that resistance is as important an issue in the community as it is in hospitals. With few exceptions, the prevalence of resistance was fairly uniform across disease states. The antibiotics most likely to encounter clinically resistant isolates during the treatment of community-acquired respiratory tract infections were penicillins, macrolides, and trimethoprim/sulfamethoxazole. The antibiotics least likely to encounter resistance were quinolones, followed by ceftriaxone and amoxicillin/clavulanate.