Epidemiologic studies of nosocomial bacterial pneumonia in patients requiring mechanical ventilation have been limited because of the poor reliability of diagnosis procedures in this setting. To determine prognostic and descriptive factors of ventilator-associated (V-A) pneumonia, we prospectively studied 567 patients who had been receiving mechanical ventilation for more than 3 days in our unit. Fiberoptic bronchoscopy using a protected specimen brush (PSB) was performed on each patient suspected of having pneumonia because of the presence of a new pulmonary infiltrate and purulent tracheal secretions. The diagnosis of V-A pneumonia was retained only if PSB specimens yielded > 103 cfu/ml of at least one microorganism, unless this result was established to be a false positive result on follow-up. V-A pneumonia developed in 49 patients for a total of 52 episodes (9%). The actuarial risk of V-A pneumonia was 6.5% at 10 days, 19% at 20 days, and 28% at 30 days of ventilation. Patients with pneumonia were significantly older (65 versus 57 yr of age, p < 0.01) and more frequently had severe underlying illnesses (24 versus 10%, p < 0.01) than did patients without pneumonia. A total of 84 microorganisms (51 gram-negative and 33 gram-positive) were isolated in significant concentrations from PSB specimens. Pseudomonas aeruginosa and Staphylococcus aureus were involved in 31 and 33% of these pneumonias, respectively. Forty percent of all specimens yielded a polymicrobial flora with more than one potential pathogen. Prior antimicrobial therapy increased the rate of pneumonia caused by P. aeruginosa or Acinetobacter spp. (65 versus 19%, p < 0.01) and the frequency of methicillin resistance in staphylococcal infections (100 versus 33%, p < 0.05). Overall mortality in patients with V-A pneumonia was 71% compared with 29% in patients without pneumonia (p < 0.01). Only 13% of patients with pneumonia caused by P. aeruginosa or Acinetobacter spp. survived, whereas 31% of patients with pneumonia caused by other bacteria survived (p < 0.01).