We evaluated the plasma homocysteine (tHcy) and nitric oxide metabolites (nitrite plus nitrate; NOx) data of consecutive patients undergoing diagnostic coronary angiography (n = 79) with respect to the presence and severity of coronary artery disease (CAD), the presence of acute coronary syndromes (ACS), and the risk status of patients. Hyperhomocysteinemia (> 15 mu mol/L) was detected in 11% of the controls (n = 19) and 37% of CAD patients (n = 60) (p = 0.03). Plasma tHcy in CAD patients was not significantly different from controls, but those with 3-vessel disease had a significantly higher tHcy concentrations than did controls (p = 0.049). The patients with 3-vessel disease and ACS had the highest concentrations of tHcy (16.9 +/- 4.4 mu mol/L), and the difference from the ACS patients with land 2-vessel involvement was significant (p = 0.03). In patients with I-vessel involvement, tHcy was correlated with NOx (r = 0.62, p = 0.005); in patients with 2- and 3-vessel disease this correlation could not be observed. The high-risk patients (n = 51) had a higher mean number of vessel involvement and tHcy (p < 0.001, p < 0.05, respectively) but lower NOx (p < 0.05) when compared to the low-risk patients (n = 28). It appears that in the early stages of atherosclerosis hyperhomocysteinemia causes an increase in NOx production, but with progression of the disease this compensatory increase disappears.