Study objectives: We hypothesized that micronutrient antioxidant intake mal be one factor determining the development of significant COPD. Vitamin E was administered to smokers to determine if exhaled ethane was reduced and if ethane correlated with measures of lung function. Study design: Longitudinal placebo lead-in trial with posttreatment observation period, Setting: Tucson Veterans Affairs Medical Center, Participants: Twenty-nine current stable smokers having no interest in smoking cessation, Interventions: Spirometry, exhaled breath ethane measurements, and vitamin E and beta-carotene plasma levels followed by 3 weeks of placebo with repeat plasma vitamin levels and ethane measurements; next, 3 weeks of vitamin E (dl-alpha-tocopherol), 400 IU po bid followed by plasma vitamin levels and breath ethane measurements; finally, 3 weeks without vitamins followed by breath ethane and plasma vitamin levels, Results: Vitamin E treatment did not reduce ethane significantly, Exhaled ethane levels (mean + SD: pm/min/kg) were as follows: baseline, 7.39 +/- 5.39; after run-in period, 6.86 +/- 4.09; after vitamin E, 6.36 +/- 3.02; and final, 7.23 +/- 4.63. After vitamin E therapy, a significant negative correlation existed between exhaled ethane and FEV1/FVC. Pack-years of smoking at baseline and after vitamin E were significantly associated with ethane exhaled, Initial lung function was not significantly negatively associated with vitamin E-induced changes in exhaled ethane but a negative trend was found. Conclusions: Vitamin E alone, unlike the combination of vitamins C, E, and beta-carotene, failed to reduced exhaled ethane in cigarette smokers. Exhaled ethane was correlated with pack-years of smoking. Smokers whose ethane values were found to fall the most tended to hale better preserved lung function.