Nosocomial bacterial pneumonia as a complication of acute, diffuse lung injury may be difficult to distinguish clinically from other pathologic processes. To determine the reliability of findings commonly used to diagnose pneumonia in this setting, we compared clinical predictions of bacterial pneumonia with postmortem histology. Pneumonia was present histologically in 58 percent of the study patients, 36 percent of whom had been thought to have only lung injury. Among patients who had only diffuse lung injury histologically, 20 percent were thought to have pneumonia by clinical evaluation. Overall, 29 percent of cases were misdiagnosed. Improved diagnostic techniques will be required before the efficacy of preventive or therapeutic measures for pneumonia in the setting of acute, diffuse lung injury can be accurately determined.