Subjects with asthma have higher concentrations of exhaled nitric oxide (NO) than normal individuals. It has been demonstrated that in asthmatics, repeated FVC maneuvers reduce NO. Although the cause of this phenomenon is not known, it has been hypothesized that deep breaths associated with FVC maneuvers reduce exhaled NO by affecting neural sources of NO, possibly via a mechanism related to the pathobiology of asthma. To establish whether FVC maneuvers influence NO concentrations in normal individuals, we measured exhaled NO at baseline values and after FVC maneuvers performed every 15 min for 1 h in subjects without asthma. To investigate the role of deep breaths in reducing exhaled NO, we compared these results with concentrations of exhaled NO after plethysmography. Repeated FVC maneuvers over 60 min produced a decrease in NO concentrations in mixed expired gas (F(E)NO; 24.6 +/- 5.1% decrease for F(E)NO, p < 0. 01 versus baseline). In contrast to the results after spirometry, repeated specific airway conductance (sGaw) maneuvers do not have a significant effect on F(E)NO (p = 0.16). These results, which demonstrate that in nonasthmatic subjects FVC maneuvers-but not panting maneuvers-produce a fall in NO, suggest that the mechanism responsible for the reduction in exhaled NO after FVC maneuvers is related to volume history of the lung rather than the pathobiology of asthma.