Cardiovascular disease is the leading cause of death in men in the UK, with atherosclerosis as the major underlying cause. Atherosclerosis is a chronic inflammatory disease and it has been documented that men with angina and heart failure often have lower levels of circulating testosterone (Eckardstein & Wu 2003). Evidence from clinical trials has shown that testosterone replacement therapy can improve symptoms of cardiovascular disease, thus indicating a potential role of testosterone as anti-inflammatory therapy in atherosclerosis (Pugh et al 2004). Fractalkine (CX3CL1) is a novel member of the chemokine superfamily and exists as two distinct forms, a membrane-bound adhesion molecule and a cleaved peptide chemotactic for cells expressing its receptor (CX3CR1). Evidence suggests that fractalkine plays a role in atherogenesis, and analysis of atherosclerotic lesions by immunocytochemistry has demonstrated its presence (Greaves et al 2001). Fractalkine is expressed on the surface of vascular cells and has been found to be up-regulated by pro-inflammatory cytokines in vitro, suggesting a role in the onset of atherosclerosis (Ollivier et al 2003, Chapman et al 2000). In order to assess whether testosterone has a modulatory effect on fractalkine expression following pro-inflammatory cytokine treatment, cell culture models have been used. Primary human aortic endothelial (HAEC) and smooth muscle cells (HASMC) cultured at 1×10⁵ cells/ml between passages 3-8 were used to investigate in vitro production and expression of fractalkine following treatment with TNF-α and IFN-γ (0-100ng/ml) for up to 48 hours. Preliminary data obtained through immunocytochemistry, confocal microscopy, RT-PCR and ELISA supports the up-regulation of fractalkine under inflammatory conditions. Anti-inflammatory effects of testosterone in this in vitro system would provide further support for the use of testosterone therapy in patients with cardiovascular disease.