Insulin resistance syndrome (IRS) is a cluster of prevalent conditions including glucose intolerance, hypertension and dyslipidemia, which commonly predispose to cardiovascular disease. However, the mechanism by which IRS is related with cardiovascular disease is not yet settled. Recently, it has been hypothesized that atherosclerosis is an inflammatory disease and that an increase in oxidative stress plays a key role in causing endothelial dysfunction associated with atherosclerosis. There has been, however, no study directly relating IRS with oxidative stress in human subjects. We measured various markers of oxidative stress among subjects who participated in a population-based epidemiological study performed in 1996. IRS was defined as non-diabetic subjects having more than two of three salient features of the syndrome (glucose intolerance, hypertriglyceridemia/low high density lipoprotein (HDL)-cholesterol and hypertension). The subjects with IRS (n=70) showed higher plasma malondialdehyde (MDA; 2.10+/-1.43 vs. 1.63+/-1.21 micromol/ml, P=0.009), homocysteine (16.32+/-8.34 vs. 13.06+/-6.49 micromol/l, P=0.002) and ceruloplasmin concentrations (29.80+/-5.28 vs. 27.39+/-5.10 mg/dl, P=0.002) than control subjects (n=196). Plasma MDA concentration was positively correlated with waist-to-hip ratio (r=0.124, P=0.044), and with plasma triglyceride (TG; r=0.163, P=0.008), ferritin (r=0.200, P=0.002) and homocysteine concentrations (r=0.136, P=0.032). These results suggest that increase in oxidative stress may contribute to the development of cardiovascular disease in IRS.