Activation of T-cells and macrophages may play a role in the pathogenesis of atherosclerosis. Therefore, serum concentrations of the immune activation markers neopterin and soluble interleukin-2 receptor were compared with routine laboratory parameters, candidate risk variables and degree of carotid atherosclerosis. Study subjects were 561 individuals (293 men and 268 women) aged between 50 and 79 years who were enrolled in a cross-sectional community based study (Ischemic Heart Disease and Stroke Prevention Study, Bruneck, Italy). Extent of carotid atherosclerosis was quantitated by an ultrasound B-mode procedure based scoring system. Detailed physical examination and quantification of laboratory and candidate risk variables were performed. By univariate as well as multivariate statistical analyses, serum concentrations of neopterin but not soluble interleukin-2 receptor were significantly higher in subjects with carotid atherosclerosis (men, 8.5 +/- 2.7 nmol/l neopterin; women, 9.6 +/- 3.3) than in those without (men, 6.7 +/- 2.3, P < 0.0001; women, 7.5 +/- 2.3, P < 0.0001). The data show that the macrophage-derived immune activation marker neopterin is closely correlated with the extent of carotid atherosclerosis. Chronic activation of immune cells, preferentially of macrophages, may play a key role in atherogenesis and/or progression of atherosclerosis.