In recent years, vascular inflammation, marked by activated monocytes and endothelium, has been proven to play a significant role in the pathogenesis of vasoocclusive 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.