The purpose of the study was to compare exhaled nitric oxide (NO) determined by three techniques. Ninety-one subjects performed a slow vital capacity maneuver: (1) through the mouth directly into a NO chemiluminescence analyzer (peak oral NO), (2) through the mouth into a collection bag (mean oral NO), and (3) through the nose into a collection bag (mean nasal NO). Peak oral NO was higher in patients with asthma (n = 18, 174.2 +/- 27.0 ppb), but lower in smokers (n = 36, 39.6 +/- 4.8 ppb) compared with nonsmoking control subjects (n = 23, 105.5 +/- 8.4 ppb, p < 0.05 both comparisons). Mean oral NO levels were significantly lower than peak oral NO levels (p < 0.05), but still higher in patients with asthma in comparison with nonsmoking healthy control subjects and asymptomatic smokers (27.2 +/- 3.5 versus 14.5 +/- 1.1 and 7.3 +/- 0.7 ppb, respectively, p < 0.05). In contrast, there was no significant difference in mean nasal NO levels between the three groups. Peak oral NO and mean oral NO levels correlated (r = 0.772, p < 0.0001). Determination of exhaled oral NO levels is qualitatively independent of the technique used, but nasal exhalation may affect NO determination in conditions associated with airway inflammation.