An imbalance between oxidants and antioxidants is proposed in smokers and in patients with airways diseases. We tested this hypothesis by measuring the Trolox equivalent antioxidant capacity (TEAC) of plasma and the levels of products of lipid peroxidation as indices of overall oxidative stress. The plasma TEAC was markedly reduced (0.66 +/- 0.07 mmol/L; mean +/- SEM; n = 11), with increased levels of lipid peroxidation products, in healthy chronic smokers as compared with healthy nonsmokers (1.31 +/- 0.10 mmol/L, n = 14, p < 0.001), an effect that was exaggerated in those who had smoked 1 h before the study. Plasma TEAC was also low in patients presenting with acute exacerbations of chronic obstructive pulmonary disease (COPD) (0.46 +/- 0.10 mmol/L, n = 20, p < 0.001) or asthma (0.61 +/- 0.05 mmol/L, n = 9, p < 0.01) with increases in plasma lipid peroxidation products. There was a negative correlation between superoxide anion release by stimulated neutrophils and plasma antioxidant capacity (r = -0.73, p < 0.001) in patients with acute exacerbations of COPD. The profound decrease in TEAC was associated with a decreased plasma protein sulfhydryl concentrations in acute exacerbations of COPD but not in smokers or in asthmatic subjects. Therefore smoking, acute exacerbations of COPD, and asthma are associated with a marked oxidant/antioxidant imbalance in the blood, associated with evidence of increased oxidative stress. The decreased antioxidant capacity in plasma may result from different mechanisms in these conditions.