Over a 5-yr period, from January 1985 to January 1990, we prospectively studied 300 episodes of nosocomial pneumonia in a 1,000-bed teaching hospital. All cases had an accurate bacteriologic diagnosis obtained by means of highly reliable techniques. Legionella pneumophila caused a total of 36 episodes; 22 were endemic and 14 occurred during an epidemic outbreak. No patient with Legionella pneumonia had been intubated before infection. To identify risk factors for nosocomial L. pneumophila pneumonia, we compared the 22 endemic cases of nosocomial pneumonia due to L. pneumophila with the 264 cases due to other bacteria. After adjusting for other variables by means of logistic regression analysis, cytotoxic chemotherapy (OR = 5.2; 95% CI, 1.5 to 17.9) and use of corticosteroids (OR = 4.6; 95% CI, 1.5 to 14.1) were positively associated with L. pneumophila pneumonia, whereas previous antibiotic therapy (OR = 0.2; 95% CI, 0.1 to 0.8) and lowered consciousness (OR = 0.2; 95% CI, 0.07 to 0.8) were negatively associated. The major risk factors for Legionella pneumonia delineated in this study should be considered in the clinical approach to and empiric therapy of patients with suspected nosocomial pneumonia.