Reactive oxygen species (ROS) are produced by phagocytic cells as part of host defense mechanisms, but these same products released by air space cells have been shown to contribute to pulmonary inflammation in interstitial lung diseases and likely represent a general mechanism of lung injury. However, the possible contribution of these compounds to lung inflammation in hypersensitivity pneumonitis (HP) has yet to be reported. We performed 11 bronchoalveolar lavage (BAL) studies in six patients with HP and compared the results with results from studies in 21 healthy normal volunteers. In patients with HP, spontaneous and stimulated measures of ROS metabolism by air space cells were significantly higher than those seen in normal volunteers. When alveolar macrophages were purified by depleting neutrophils and eosinophils on density gradients of Percoll (specific gravity 1.075 gm/ml), ROS metabolism remained elevated when compared with that in cells obtained from healthy controls, confirming that alveolar macrophage ROS metabolism is enhanced in patients with HP. Further, we found significant elevations in BAL total protein, lymphocytes, eosinophils, and neutrophils in patients with HP when they were compared with normal volunteers, with an increased proportion of BAL T lymphocytes expressing CD8 and natural killer surface antigens, consistent with previous work. Lavage samples from patients with HP with clinically active disease had higher proportions of BAL eosinophils and concentrations of total protein, lower forced expiratory volume in 1 second, lower forced vital capacity, and lower arterial oxygen tensions, and higher indices of ROS metabolism than samples from patients with HP with inactive disease. HP is associated with evidence of air space inflammation, to which alveolar macrophage-derived ROS may contribute.