We conducted a double-blind randomized study to determine the effect of vitamin C on NO2-induced airway hyperresponsiveness in normal subjects. Eleven normal subjects were randomly assigned an order for 4 experimental exposures. For each exposure, subjects took either vitamin C (500 mg 4 times a day for 3 days) or placebo followed by exposure either to clean air or to 2.0 ppm NO2. Measurements of lung mechanics and airway responsiveness to methacholine aerosol were obtained. Serum level of ascorbic acid was determined before each exposure. NO2 exposure with placebo resulted in significant enhancement of airway responsiveness to methacholine aerosol (air-placebo 64 +/- 7 to NO2-placebo 53 +/- 8 mg/ml). Pretreatment with ascorbic acid prevented the significant alteration in airway responsiveness to methacholine aerosol (65 +/- 13 mg/ml, p less than 0.04). These results suggest that airway hyperresponsiveness induced by NO2 in normal subjects is completely prevented by pretreatment with ascorbic acid.