Previous studies have raised the possibility that the measurement of nitric oxide (NO.) concentrations in expired air may represent a noninvasive measure of lower airway inflammation. To address the question of whether the elevated NO. recovered in mixed expired air from asthmatic subjects is a reflection of the pulmonary airway microenvironment or merely nasopharyngeal contamination, mixed expired NO. determinations were performed in five normal and five asthmatic subjects before and after orotracheal intubation (thereby isolating the lower airway gas from ambient air contamination or gas conditioned in the nasopharynx). The mixed expired NO. concentrations determined in patients with asthma were significantly elevated (p < 0.05 or less) above those of normal subjects in both the pre- and postintubation samples. After intubation, mixed expired NO. levels were 4.7 +/- 1.3 ppb and 13.2 +/- 2.0 ppb in normal and asthmatic individuals, respectively; the difference in these values was statistically significant (p < 0.01). Lower airway gas, sampled through the bronchoscope during a breathhold, was found to contain NO. concentrations of 7.0 +/- 1.2 ppb and 40.5 +/- 5.6 ppb at the tracheal carina of normal and asthmatic individuals, respectively. The asthmatic values were significantly (p < 0.01) elevated above those found in normal subjects. These findings indicate that the difference in mixed expired NO. of normal subjects and asthmatics reflects a difference in NO. concentration present in the lower airway.