Systemic inflammation plays a key role in atherosclerosis and occurs in the vasculature as a response to injury, lipid peroxidation, and perhaps infection. Levels of circulating soluble adhesion molecules, which mediate adhesion of leucocytes to the vascular endothelium, are elevated in patients with obstructive sleep apnoea syndrome (OSAS) and improve with CPAP therapy. Inflammatory cytokines, such as the nuclear factor kappa B (NFkB) dependent genes tumour necrosis factor alpha (TNFa) and interleukin-8 (IL-8) induce the expression of cellular adhesion molecule and TNFa levels correlate with cardiovascular risk. In a novel cell culture model of intermittent hypoxia/reoxygenation (IHR), which is a key feature of OSAS, we identified a selective activation of inflammatory pathways, mediated by the transcription factor NFkB, over the adaptive hypoxia-inducible factor-1 (HIF-1)-dependent pathways by IHR (1). These results indicate different molecular responses of IHR than to sustained hypoxia, the latter being primarily mediated by a HIF-1 mediated phenotype to promote tissue survival. We translated these in vitro findings into the OSAS population and demonstrated higher levels of TNFa in OSAS patients than in matched controls but similar levels of the adaptive factor erythropoietin (EPO). Furthermore, CPAP treatment reduced TNFa to control levels (2). C-reactive protein (CRP), an important serum marker of inflammation, is synthesised in the liver and regulated principally by IL-6. Prospective studies have shown that CRP is a predictor of future coronary events in apparently healthy men and women. OSAS is associated with higher CRP and IL-6 levels in otherwise healthy subjects, and levels correlate with severity of the disease. Furthermore, treatment with nasal CPAP significantly decreases levels of these markers. However, other studies have indicated that obesity is an important confounding factor in the elevation of CRP and IL-6 in OSAS patients (3). The intermittent re-oxygenation seen in OSAS has been compared to reperfusion injury and predisposes to oxidative stress with the production of increased quantities of reactive oxygen species (ROS). The evidence for oxidative stress in OSAS is based on the demonstration of increased ROS production by leucocytes taken from patients with OSAS and in rodents exposed to intermittent hypoxia, and also by the demonstration of reduced ROS production following CPAP therapy. Furthermore, evidence of oxidation of various macromolecules, particularly lipid peroxidation, in OSAS patients provides further evidence of oxidative stress. Endothelial dysfunction is considered an early marker for atherosclerosis and its role in the pathogenesis of cardiovascular complications in OSAS has been supported by various studies demonstrating impairment in endothelium-dependent vasodilatation. Furthermore, treatment with nasal CPAP improves endothelial function. A major vasodilator substance released by the endothelium is nitric oxide (NO). Decreased production or activity of NO may be one of the earliest signs of atherosclerosis. Decreased levels of NO have been found OSAS patients and levels increase with CPAP therapy. We have also demonstrated significant involvement of NO in NFkB activation by IHR in our in vitro model. Thus, the prevention IHR in OSAS may result in prevention of inflammatory activation and thus may explain, in part, the reduction of cardiovascular risk in OSAS patients on treatment (4).