To investigate the role of oropharyngeal and cutaneous commensal microorganisms (OCCs) as a cause of ventilator-associated pneumonia (VAP). Retrospective analysis of the medical and microbiological records. One medical-surgical ICU. All VAP episodes recorded during a 10-year period were reviewed. All patients with suspected VAP underwent bronchoscopy with protected-specimen brush (PSB) sampling and BAL before any change in antibiotic therapy was made. OCC-VAP was defined as VAP with significant growth in quantitative cultures (PSB yielded > or = 10(3) cfu/mL and/or BAL yielded > or = 10(4) cfu/mL) of OCCs only. Three experts reviewed the episodes. Exposed patients (ie, those with OCC-VAP) and unexposed patients (ie, patients without VAP) matched on condition severity at ICU admission and mechanical ventilation duration were compared. Twenty-nine episodes in 28 patients with > or = 10(4) cfu/mL OCCs in BAL fluid and/or > or = 10(3) cfu/mL OCCs in PSB specimens were found. All patients in these episodes had new radiologic lung infiltrates, with 26 episodes involving purulent tracheal aspirates, 23 episodes involving temperatures > or = 38.5 degrees C, and 18 episodes involving > or = 11,000 leukocytes/ microL. The main OCCs found were non-beta-hemolytic Streptococcus spp (n = 12), Neisseria spp (n = 7), and coagulase-negative Staphylococcus spp (n = 6). Other possible reasons for fever and the presence of new chest infiltrates were found in 20 and 17 patients, respectively. Histologic evidence of pneumonia was found in 2 of the 10 patients who died. The three experts agreed on the diagnosis for 23 patients. In the OCC-VAP group only, the mean (+/- SD) logistic organ dysfunction (LOD) scores increased significantly (LOD score, 2 +/- 4; p = 0.008) during the 3 days before bronchoscopy, and ICU stay duration was longer than in the unexposed group. The exposed/unexposed study found no difference in mortality. OCCs may behave like classic nosocomial pathogens in critically ill patients.