The objective of this prospective study was to determine positive isolation rates for potential respiratory pathogens (PRPs) in the naso- and oropharynx of adults hospitalized for nonpneumonic lower respiratory tract infection (NPLRTI), compared with patients with community-acquired pneumonia (CAP) and healthy controls. The study population was 315 non-chronic obstructive pulmonary disease adults hospitalized with febrile lower respiratory tract infection (158 NPLRTI and 157 CAP) and 450 control subjects. Each participant was sampled by oropharyngeal swab, nasopharyngeal swab, and nasopharyngeal washings that were tested by conventional bacteriologic methods to identify PRP. At least 1 of the samples was positive for at least 1 of the 3 PRP bacteria in 55 NPLRTI patients (35%) compared with 51 CAP patients (33%) (NS) and 100 controls (22%) (P = 0.003 compared with NPLRTI and P = 0.02 compared with CAP). Samples were positive for Streptococcus pneumoniae in 14 NPLRTI patients (9%) compared with 29 CAP patients (19%) (P = 0.02) and 16 controls (4%) (NPLRTI P = 0.015, CAP P < 0.0001). The corresponding rates for Haemophilus influenzae were 23 (15%), 16 (10%), and 60 (13%) (NS for all 3 comparisons), and for Moraxella catarrhalis, 28 (18%), 25 (16%), and 48 (11%), respectively (NPLRTI versus controls, P = 0.03, NS other comparisons). We conclude that the rate of positive naso/oropharyngeal isolates for at least 1 of the 3 PRP bacteria in NPLRTI patients is similar to the corresponding rates for CAP patients and is higher in both groups than in controls.