Elevated levels of C-reactive protein are one of the strongest prognostic factors in atherosclerosis. In addition to predicting vascular disease, C-reactive protein may directly facilitate the development of a proinflammatory and proatherosclerotic phenotype. Recent studies have demonstrated marked up-regulation of various adhesion molecules and inflammatory responses in endothelial cells subjected to C-reactive protein. The nuclear factor-κB signal transduction is known to play a key role in the expression of these proatherogenic entities. This study examines the direct effects of C-reactive protein on nuclear factor-κB activation and related mechanisms in saphenous vein endothelial cells.