The SENTRY Antimicrobial Surveillance Program has been monitoring the activity of commonly prescribed and novel antimicrobial agents on a global scale from 1997 to the present. Specific objectives have documented the key resistance rates among pathogens from both patients hospitalized with pneumonia and those diagnosed with community-acquired pneumonia. Hemophilus influenzae and Streptococcus pneumoniae are common pathogens in both of these patient populations and the susceptibility profiles for these two species were compared to distinguish potential differences that may be evident in North American surveillance (1997-2001). A total of 6,515 isolates of S. pneumoniae and 6,726 H. influenzae strains were tested using reference broth microdilution methods at a monitoring center. Ampicillin resistance was approximately 25% among H. influenzae isolates and did not significantly differ between strains from community-acquired infections or hospitalized patients. beta-lactamase-negative ampicillin resistant strains and fluoroquinolone refractory strains were rare (0.3 and </= 0.2%, respectively) and the former only detected among hospitalized patients. Macrolide-resistant H. influenzae was most prevalent in hospitalized patients with pneumonia (24.4% for clarithromycin). In contrast, H. influenzae isolates from community-acquired infections were less susceptible (78.6-81.7%) to trimethoprim/sulfamethoxazole, but very susceptible to fluoroquinolones (99.9-100.0%). The community-acquired S. pneumoniae isolates were generally more resistant to penicillin (16.7%) and other beta-lactams compared to those from hospitalized patients (12.1%), and were also much more resistant to trimethoprim/sulfamethoxazole (25.0%) compared to inpatient isolates (6.7%). In contrast, isolates with reduced fluoroquinolone susceptibility or resistance were more common among hospitalized patients (ciprofloxacin resistance at 4.0%) and increased over the five monitored years. It is evident from this longitudinal study that some antimicrobial agents are becoming less efficacious against common respiratory tract pathogens depending on the clinical setting and surveillance of resistance appears to be a prudent practice.