The purpose of this study was to determine the microbial etiology of pneumonia by using strict criteria among a group of hospitalized patients. Patients with acute community-acquired or hospital-acquired pneumonia were studied in a systematic and comprehensive manner for bacterial, viral, chlamydial, mycobacterial, and fungal pathogens. A total of 198 patients with 204 episodes of pneumonia were evaluated. Despite 100 percent follow-up of all surviving patients, a specific etiologic agent could be found in only 103 episodes. Among 154 episodes of community-acquired pneumonia, a diagnosis was made in 79; the most common pathogen was from the genus Legionella, followed by various Gram-negative enteric bacteria, Gram-positive cocci, influenza A virus, and Mycoplasma pneumoniae. The etiologic agent was found in 24 of the 50 patients with hospital-acquired pneumonia; no pathogen predominated. We conclude that even when elaborate diagnostic studies are done, including many invasive procedures, the etiology can be determined in only about half of the patients with acute pneumonia. The pathogens of pneumonia in this study are not markedly different between community-acquired and hospital-acquired infection.