In recent years, vascular inflammation, marked by activated monocytes and endothelium, has been proven to play a significant role in the pathogenesis of vaso-occlusive events (VOEs) in sickle cell disease (SCD). Vascular endothelial growth factor (VEGF), an endothelial cell mitogen, has been shown to contribute to the increased endothelial cell adhesivity by increasing the expression of cell adhesion molecules ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) on the endothelium. We have investigated VEGF alterations in 37 patients with SCD during VOEs and/or steady state. VEGF levels (mean±SEM) were found to be significantly elevated during VOEs (703.1±119.0 pg/ml) when compared with those at steady state (258.0±57.8 pg/ml) and healthy controls (196.6±21.9 pg/ml) (p<0.001). However, we did not find a difference between VEGF concentrations in sickle patients at steady state and the normal subjects (p>0.05). We suggest that considering a possible stimulatory role of tissue hypoxia in VEGF production during VOEs, VEGF levels in sickle patients might be helpful in monitoring disease severity.