While increased concentrations of C-reactive protein (CRP) are associated with increased vascular risk, little information is available describing genetic determinants of this effect. In a large prospective cohort of apparently healthy men, we found plasma CRP concentrations to be significantly reduced among carriers of a 1059G/C polymorphism in the human CRP gene (GC or CC) as compared with non-carriers (GG). However, the polymorphism examined was not significantly associated with risk of arterial thrombosis despite the fact that CRP concentrations are a potent independent predictor of future vascular events in this cohort. These data suggest that genetic and environmental determinants each importantly contribute to the vascular risk associated with inflammation.