Ozone (O3) is a major constituent of urban air pollution. The acute effects of the inhalation of O3 at ambient or near-ambient concentrations on bronchoalveolar lavage (BAL) end points consistent with a distal lung inflammatory response have been well documented in human subjects. Animal toxicologic studies have shown that the airway is also a major site of O3-induced injury and inflammation. To date, no studies have confirmed this finding in human subjects. Effects of O3 on the proximal airways are not adequately studied by BAL, which is primarily influenced by events occurring in the terminal bronchioles and alveoli. We hypothesized that O3 causes injury and inflammation in the airways in addition to that previously documented to occur in the distal lung. We performed isolated lavage of the left mainstem bronchus and forceps biopsy of the bronchial mucosa in a group of 14 healthy, athletic subjects 18 h after exposure to 0.20 ppm O3 for 4 h during moderate exercise in order to assess this possibility. We followed an identical protocol in a similar group of 12 subjects exposed to filtered air. The mean (SD) total cell count and the lactate dehydrogenase (LDH) concentration in the isolated airway lavage were significantly greater after O3 than after air, 13.9 (20.5) versus 4.9 (5.4) cells/ml × 104 and 18.9 (11.2) versus 9.6 (9.0) U/L, respectively. Morphometry (2,070 neutrophils/cm2 of tissue for O3 and 330 neutrophils/cm2 of tissue for air) demonstrated that O3 exposure induced an acute inflammatory cell influx into the airway. These data demonstrate that inhalation of an ambient concentration of O3 can cause morphologic evidence of airway injury in healthy human subjects. Ozone-induced airway inflammation may be an important contributing factor to acute exacerbations of asthma and chronic bronchitis.