Because inflammation stimulates the expression of inducible nitric oxide (NO) synthase (iNOS) with an associated increased local NO production, we hypothesized that patients with pneumonia would have increased excretion of NO into their airways. To test this hypothesis, NO was measured in the exhaled air and from the nasal cavities of 49 consecutively intubated and mechanically ventilated patients in our ICU. After excluding NO gas contamination in the inspiratory circuit, nasal NO and end-expiratory and mean exhaled tracheal NO levels and plasma nitrate concentrations were measured using a fast response chemiluminescence analyzer. Twenty-one patients (43%) presented with infectious pneumonia. End- expiratory exhaled NO concentrations were significantly higher in patients with pneumonia as compared with patients without pneumonia (5.9 +/- 1 ppb versus 3.2 +/- 0.5 ppb, p < 0.01). Similarly, mean nasal NO was higher in patients with pneumonia (1039 +/- 138 ppb versus 367 +/- 58 ppb, p = 0.003). Plasma nitrate levels did not differ between patient groups. Threshold values of tracheal or nasal NO were defined and subsequently validated in 60 other patients. Positive and negative values of a maximal tracheal level > 5 ppb for pneumonia were 74% and 89%, respectively. Thus tracheal and nasal NO levels may be of help in distinguishing patients with acute pneumonia from other causes. Furthermore, because these differences in airway NO levels were not paralleled in blood nitrite concentrations, we conclude that pneumonia per se is not associated with systemic NO production.