The upper airway, especially the nose, is a major target of toxic damage. Nasal challenges followed by nasal lavage (NAL) have been applied to studies of hypersensitivity, in particular as a method to identify the allergen in patients with allergic situations such as rhinitis. The NAL method has not been extensively used to determine the effects of air pollutants on the upper airways in humans. Ozone is known to interact avidly with various tissues in the respiratory tract and to cause decrements in lung function tests. This oxidant pollutant has also been shown to induce inflammation in the lower airways of humans and animals. In this study, we have examined the effect of an acute (2 h) exposure of ozone at 0.4 ppm on the inflammatory response in the upper airways of 10 normal volunteers and compared these results to those obtained in the lower airways assessed by bronchoalveolar lavage (BAL). The results indicate significant increases in the number of polymorphonuclear neutrophils (PMN) in NAL immediately post exposure (7.7-fold). This increase is still detectable 18 h post exposure (6-fold) which is similar to the increase of PMN in BAL. Tryptase, released by mast cells was also increased in the NAL fluid immediately post exposure (2-fold). While the albumin level, which is an indicator of epithelial cell permeability, was elevated 18 h post exposure (1.5-fold), tryptase level, was not anymore elevated at that time point. Interestingly, several other markers of acute inflammation such as prostaglandin E2 (PGE2), C3a, urokinase-type plasminogen activator (U-PA), which were found to be significantly elevated in the BAL of the same group of subjects (18 h post exposure), were not elevated in the NAL either immediately post or 18 h post exposure. The level of uric acid, thought to be an important anti-oxidant molecule, was also unchanged in the NAL fluid but was elevated in the BAL fluid. Collectively the data suggest that NAL may serve as a sensitive and reliable technique to detect inflammation in the upper airways of subjects exposed to ozone. Moreover, in the case of this particular oxidant pollutant, the NAL seems to mirror the inflammatory response in the lower airways, 18 h post exposure, relative to the number of PMN and albumin levels.