Heme oxygenase (HO) is considered to be an antioxidant enzyme that catabolizes heme to produce carbon monoxide (CO) and biliverdin. We determined the expression and distribution of HO-1 and HO-2, two isoenzymes of HO, in the airways of patients with asthma, and determined the effect of inhaled corticosteroid therapy. Immunostaining for both enzymes was widely distributed in the airways' submucosa, particularly in airway epithelium and submucosal macrophages (CD68(+)) as determined by double immunostaining. There was no difference in intensity and extent of staining in biopsies from normal subjects (n = 10) and subjects with asthma (n = 10). Following 1 mo of treatment with inhaled corticosteroids (budesonide 1,600 microg/d), there was no significant change in the expression and distribution of either HO-1 or HO-2 in the airways' submucosa in eight subjects with mild asthma, despite a significant reduction in airway eosinophils and a reduction in bronchial responsiveness to methacholine. Levels of exhaled nitric oxide were significantly reduced, but exhaled CO levels remained unchanged by the treatment. Treatment with a placebo inhaler (n = 8) had no effects on these parameters. Thus, both HO-1 and HO-2 are extensively distributed equally in normal subjects and subjects with asthma, and are not modulated by inhaled corticosteroid therapy in subjects with asthma. HO may be an important endogenous antioxidant enzyme.