An arteriovenous fistula (AVF) is a vein graft which is created to permit access to the bloodstream allowing haemodialysis to be performed in renal failure patients. An AVF is considered the best option in clinical practice; however a significant failure rate is still reported, with as little as 50% remaining patent at 6 months (Field et al., 2008). Failure of these grafts is largely due to vascular smooth muscle cell (VSMC) hyper-proliferation, leading to the development of neointima which invades the lumen causing stenosis and impaired blood flow (Lee and Roy-Chaudhury, 2009). Inflammation is known to play a key role in the development of vascular stenosis; although the exact mechanisms and triggers are not fully known. The aims of this study were to 1) evaluate the changes undergone in VSMC present within human failed AVF vs. non-stenosed controls, and 2) investigate the inflammatory processes upregulated in human failed AVF vs. non-stenosed controls. Histology of failed human AVF stained with H & E confirmed a significant increase in media: lumen ratio increasing from 2.2 ± 0.6 in control veins to 18.8 ± 6.9 in AVF vein sections (p<0.005, Control vs. AVF; n=8), with the majority of these cells positive for α-SMA. Toluidine blue staining of the vein wall for mast cell infiltration highlighted a 5 fold increase in mast cells within AVF vein tissues (p<0.005 Control vs. AVF; n=9, 7), with VCAM-1 also found to be expressed within the vein wall by immunohistochemistry (IHC). The percentage of cells within the stenosed vein segments undergoing proliferation, as measured by expression of PCNA using IHC, was 33.6 ± 4.9% in the AVF vs. 3.5 ± 1.5% in the control (p<0.005 AVF vs. Control; n=5, 8). VSMC were explanted from both groups of patients, and cell proliferative capacity was measured by 3H thymidine incorporation. At maximal stimulation with 10% FCS the fold increase in thymidine uptake within the AVF-derived cells was 32 times that of the non-stimulated cells, compared to a 15 fold increase within the control-derived cells (p<0.005 AVF vs. Control; n=4). The cell cycles of these explants were also investigated using propidium iodide and flow cytometry. AVF-derived explants showed a trend towards an increase in the number of cells undergoing the G2/M stages of cell cycle. These results highlight significant venous hypertrophic remodelling in human AVF-vein sections. The remodelling can be largely attributed to vascular smooth muscle cell accumulation with inflammatory cell infiltrates. In VSMC studies we have demonstrated that cells derived from the AVF have an increased capacity to proliferate.