Cultures of tracheal secretions, bronchoalveolar lavage (BAL), protected specimen brushes (PSB), and direct lung aspirates were compared with cultures of lung homogenates and histologic findings in 35 baboons after 7 to 10 days of intubation and mechanical ventilation. Six animals received no antibiotics, while the remainder were treated with a variety of prophylactic regimens of intravenous and topical agents. Bacterial contamination at each culture site was expressed as a "bacterial index" (BI), obtained as the sum of the logarithmic concentrations of individual species. In the absence of antibiotics, pneumonias occurred in all animals and were polymicrobial; 56% of organisms in lung tissue were members of the normal upper respiratory tract flora, while 44% were gram-negative bacilli with a mean total bacterial index of 13.94/g. Lobar tissue BI values greater than 6.0/g were found in 77% of lobes containing pneumonias judged by histologic criteria to be moderate or severe in extent, whereas only 7% of lobes with lesser inflammatory changes had similar BI values. The BI values of BAL were linearly related to tissue values, whether the BAL was performed of the same lobe cultured or a different lobe. BAL recovered 74% of all species present in lung tissue compared to 41% by PSB and 56% for needle aspirates. False positive specimens were found with similar frequency with these 3 procedures. Tracheal aspirates revealed 78% of organisms found in lung tissue, but 14 of 35 (40%) of species isolated were not present in lung tissue. BAL provides the best reflection of the lung's bacterial burden, both quantitatively and qualitatively, in the setting of prolonged intubation and ventilation.