We analyzed the susceptibility of low-density lipoproteins (LDL) to oxidation in 17 healthy smokers (43.3 +/- 16.8 pack-years) and 19 healthy nonsmokers, matched for age (smokers: 52 +/- 7 years; nonsmokers: 53 +/- 7 years), gender, and relative body mass. Cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, and apolipoprotein (apo) B were not different between smokers and nonsmokers; apo A-I was slightly lower in smokers (one-tailed P = 0.066). To study whether LDL from smokers were prone to in vitro oxidation than LDL from nonsmokers, we measured the time kinetics of diene formation and the production of malondialdehyde during oxidation of LDL in vitro. In smokers and nonsmokers, respectively, the mean (+/-SD) lag times (tinh) of diene formation were 111 +/- 26 and 100 +/- 27 min, the peak rates of diene formation (Vmax) were 5.99 +/- 2.34 and 6.34 +/- 2.30 mmol x min-1 x g-1, and the amounts of dienes produced during the propagation phase (dmax) were 250 +/- 264 and 248 +/- 56 mmol x g-1. Neither the malondialdehyde content of LDL (measured as thiobarbituric acid-reactive substances) before oxidation nor the amount of malondialdehyde generated during oxidation (smokers: 57.0 +/- 14.2 micromol x g-1; nonsmokers: 63.2 +/- 15.2 micromol x g-1 indicated any statistically significant effect of smoking. When nonsmokers and smokers were considered together, the amount of malondialdehyde generated during oxidation correlated with age (nonparametric rs = 0.405), body mass index (r2 = 0.573), and concentrations of apo B (rs = 0.480), cholesterol (rs = 0.448), triglycerides (rs = 0.436), and LDL cholesterol (rs = 0.398). Our data show that smoking is not associated with increased oxidizability of LDL in healthy men and women at ages 42-63 years.