Moderate hyperhomocysteinaemia is considered as an independent risk marker for cardiovascular disease and stroke. Earlier, increased homocysteine production was detected in stimulated immunocompetent cells in vitro, and several markers of inflammation like neopterin or C-reactive protein (CRP) were demonstrated as significant indicators of cardiovascular risk. The relationship between coronary artery disease (CAD), homocysteine metabolism and markers of immune activation and inflammation was investigated in a population of 1717 patients undergoing coronary angiography, recruited as participants of the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study. 1325 patients (77.2%) suffered from coronary artery disease (CAD), which was was defined as the occurrence of a visible luminal narrowing (>or=20% stenosis) in at least 1 of 15 coronary segments according to the classification of the American Heart Association, the remaining 392 individuals of the study population served as controls. Significant differences regarding systolic blood pressure, homocysteine, neopterin and folic acid concentrations were observed between patients and controls. Older age, decreased creatinine-clearance and higher concentrations of homocysteine and CRP were indicative for CAD. Low B-vitamin availability, therapy and the extent of immune activation strongly influenced homocysteine concentrations. Homocysteine concentrations were correlated with neopterin levels (r(s) =0.325, p<0.001), and hyperhomocysteinaemic patients also presented with significantly higher CRP concentrations. Homocysteine accumulation coincided with impaired renal and heart function (as reflected by ProBNP[Brain natriuretic peptide]-concentrations). We conclude that homocysteine accumulation could result from B-vitamin deficiency which is related to chronic immune activation.