Several studies have reported that elevated plasma levels of total homocysteine (tHcy) are related to an increased risk of cardiovascular disease. Only a few studies have looked at the effect of cysteine, another amino thiol, on cardiovascular disease risk. Therefore, in the present case-control study we compared plasma total cysteine (tCys) levels and plasma tHcy levels among subjects with severe coronary atherosclerosis (cases, n=131), subjects without severe coronary atherosclerosis (coronary controls, n=88) and healthy subjects (population-based controls, n=101). Cases were defined as those having > or =90% occlusion in one and > or =40% occlusion in a second coronary artery, while coronary controls had a maximum of 50% occlusion in only one coronary artery. Both males and females, aged 26--64 years were studied. We have previously reported that plasma tHcy is an independent risk factor for coronary atherosclerosis in this study population. In the present analysis, we found that cases had statistically significant higher mean plasma tCys levels than coronary controls and population-based controls (295.8+/-40.2, 279.0+/-35.5 and 282.6+/-32.4 micromol/l, respectively). The odds ratio (OR) of coronary atherosclerosis for the upper tertile of tCys compared with the bottom tertile was 2.5 (95% confidence interval (CI), 1.4--4.3). However, the association between tCys and coronary atherosclerosis was confounded to a great extent by risk factors (OR, 1.0; 95% CI, 0.5--2.0). The multivariate adjusted OR of coronary atherosclerosis per 1 S.D. increase in plasma tCys was 1.0 (95% CI, 0.8--1.3). The corresponding OR per 1 S.D. increase in plasma tHcy was 1.4 (95% CI, 1.1--1.8). We conclude that plasma tCys, unlike plasma tHcy, is not an independent risk factor for atherosclerosis.