The spectrum of pathogens and the microbiologic investigations used to obtain a diagnosis in 178 patients with severe pneumonia (88 percent requiring intermittent positive-pressure ventilation) are reviewed. Ninety-five patients had primary pneumonia, 31 had nosocomial pneumonia, 24 were immunocompromised patients, and 28 had aspiration pneumonia. While the spectrum of isolates conformed to the usual patterns for the different types of pneumonia, the incidence of Gram-positive infections (15 percent), predominantly Klebsiella pneumoniae, Staphylococcus aureus, (8 percent), and Legionella pneumophila (5 percent) in primary pneumonia was much higher than in community or general hospital-based studies, and only one case of Mycoplasma pneumoniae was identified. Gram stain of sputum or tracheal aspirate taken on intubation in primary pneumonia was reliably predictive of the causative organisms in both Gram-positive and Gram-negative infections when compared with infections proven by blood culture. Serologic studies were valuable in patients in whom no positive microbiologic diagnosis was evident; however, fiberoptic bronchoscopy contributed minimally to the microbiologic diagnosis in this group of patients. The cause of severe primary pneumonia differs from less severe disease, and this should be recognized when selecting empiric antibiotic therapy.