The human endothelial nitric oxide synthase (eNOS) gene is highly polymorphic. Evidence for the involvement of eNOS single nucleotide polymorphisms in the development of essential hypertension is limited, though the eNOS Glu298Asp polymorphism appears to influence the blood pressure response to exercise. This variant also influences endothelial function, with its effects becoming manifest during the adaptive vascular changes of pregnancy. Carriers of eNOS Asp298 may be at risk of developing pre-eclampsia. Molecular studies have indicated that intact eNOS Asp298 has equivalent enzymatic activity to eNOS Glu298, but undergoes selective proteolysis in native cells and tissues such that the steady state level of active eNOS may be reduced in carriers of this allele. Carriers of eNOS Asp298, particularly if exposed to adverse environmental infuences on endothelial function, may be at increased risk of developing atherosclerosis and cerebrovascular disease.