High total homocysteine (tHcy) concentrations increase coronary disease risk. Therefore, the authors examined the relation between tHcy concentrations and the number of stenotic arteries in patients with ischemic heart disease (IHD). They enrolled 155 patients with IHD (135 men) who had undergone selective coronary angiography during the previous 2 years. These patients were divided into 4 groups according to the number of vessels (0, 1, 2, and 3) with > or = 70% stenosis. They also reviewed the major coronary risk factors for each patient (age, gender, hypertension, diabetes mellitus, dyslipidemia, cigarette smoking, obesity), and measured serum concentrations of tHcy, folate, vitamin B12 and lipids. There was a significant positive correlation (rs = 0.19; p = 0.017; n = 155) between tHcy serum concentration and the extent of coronary atherosclerosis, expressed by the number of coronary arteries with significant stenosis. Moreover, the number of affected vessels displayed a significant positive correlation with the presence of diabetes mellitus (rs = 0.30; p < 0.0001; n = 155) and serum concentrations of lipoprotein (a) (rs = 0.25; p < 0.05; n = 67) and a negative correlation with apolipoprotein A-I serum concentration (rs = -0.27; p < 0.01; n = 67). In this study, the serum concentrations of tHcy correlated with the extent of coronary atherosclerosis, independently of other classical risk factors, with the exception of diabetes mellitus.