The Respiratory Surveillance Program (RESP) was undertaken over a 10-month period (July to April) during the 1999-2000 respiratory infection season. A total of 16,213 nasal swab samples were taken by primary care physicians in outpatient settings from patients diagnosed as having acute bacterial rhinosinusitis. The samples were sent to a central laboratory where a pathogen was identified and antibiotic susceptibilities were determined. A pathogen could be isolated from 34% of the samples submitted. Four pathogens accounted for 79.7% of all identifiable isolates: Streptococcus pneumoniae (11.3%), Haemophilus influenzae (21.7%), Moraxella catarrhalis (28.9%), and Staphylococcus aureus (17.9%). Resistance to penicillin was found for S pneumoniae (16% fully resistant, 20% intermediate resistance). S pneumoniae had a 32% to 35% rate of resistance to erythromycin, azithromycin, and clarithromycin. H influenzae showed a high rate of resistance to clarithromycin (36%). M catarrhalis had a 15% rate of resistance to erythromycin and a 91.5% rate of resistance to penicillin. Low levels of resistance were seen to the newer fluoroquinolones levofloxacin (minimum inhibitory concentration [MIC](90) = 2 microg/mL) and gatifloxacin (MIC(90) = 0.5 microg/mL), with the 4 major bacterial isolates having a 95% to 100% rate of susceptibility to these medications. The results from the RESP study can give practicing physicians vital information about pathogen profiles and susceptibilities within their communities and help them in making appropriate treatment choices for their patients with acute rhinosinusitis. Patients with previous antibiotic exposure had a higher incidence of nonsusceptible strains than patients who did not receive prior therapy.