To evaluate whether acute effects of ozone, nitrogen dioxide, and particulates with mass median diameter less than 10 micro m could be attenuated by antioxidant vitamin supplementation, we conducted a randomized trial using a double-blinded design. Children with asthma (n = 158) who were residents of Mexico City were randomly given a daily supplement of vitamins (50 mg/day of vitamin E and 250 mg/day of vitamin C) or a placebo and were followed from October 1998 to April 2000. Pulmonary function tests were carried out twice a week in the morning. During the follow-up observation period, the mean 1-hour maximum ozone level was 102 ppb (SD = 47), and the mean 24-hour average PM(10) level was 56.7 micro g/m(3) (SD = 27.4). In children with moderate and severe asthma, ozone levels 1 day before spirometry were inversely associated significantly with forced expiratory flow (FEF(25-75)) (-13.32 ml/second/10 ppb; p = 0.000), FEV(1) (-4.59 ml/10 ppb; p = 0.036), and peak expiratory flow (PEF) (-15.01 ml/second/10 ppb; p = 0.04) in the placebo group after adjusting for potential confounding factors. No association between ozone and lung functions was observed in the supplement group. We observed significant differences in lung function decrements between groups for FEF(25-75) and PEF. Our results suggest that supplementation with antioxidants might modulate the impact of ozone exposure on the small airways of children with moderate to severe asthma.