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Recent discoveries suggesting essential bioactivities of nitric oxide (NO.) in the lung are difficult to reconcile with the established pulmonary cytotoxicity of this common air pollutant. These conflicting observations suggest that metabolic intermediaries may exist in the lung to modulate the bioactivity and toxicity of NO.. We report that S-nitrosothiols (RS-NO), predominantly the adduct with glutathione, are present at nano- to micromolar concentrations in the airways of normal subjects and that their levels vary in different human pathophysiologic states. These endogenous RS-NO are long-lived, potent relaxants of human airways under physiological O2 concentrations. Moreover, RS-NO form in high concentrations upon administration of NO. gas. Nitrite (10-20 microM) is found in airway lining fluid in concentrations linearly proportional to leukocyte counts, suggestive of local NO. metabolism. NO. itself was not detected …