Inflammation plays a pivotal role in atherosclerosis. In addition to being a risk marker for cardiovascular disease, much recent data support a role for C-reactive protein (CRP) in atherogenesis. Interleukin-8 (IL-8), a member of the CXC chemokines promotes monocyte-endothelial cell adhesion and arrest and is abundant in atherosclerotic plaques. However, there is a paucity of data examining the effect of CRP on IL-8 secretion in human aortic endothelial cells (HAEC). In this report, we show that incubation of HAEC with CRP resulted in a time and dose-dependent increase in IL-8 protein and mRNA via transcription. In contrast to human umbilical vein endothelial cells, monocyte-chemoattractant protein-1 expression in HAEC was not affected by CRP. Furthermore, CRP upregulated NF-kappa B activity in HAEC and inhibitors of NF-kappa B significantly reversed the upregulation of IL-8 by CRP. Blocking antibodies to IL-8 significantly decreased monocyte-endothelial cell adhesion induced by CRP (31%, P<0.01). In conclusion, this study makes the novel observation that CRP induces IL-8 synthesis and secretion in HAEC via upregulation of NF-kappa B activity.