This study reviews recent experimental data from our own and other laboratories on the effects of hypertension on the arterial wall and the potential mechanisms by which hypertension can induce vascular injury and accelerate atherosclerosis. The findings suggest that the responses of the arterial media to hypertension reflect appropriate adaptations to increased intramural tension with resultant medial thickening secondary to an increase in both cellular mass and extracellular matrix. The role of growth factors in this process and their effects on arterial contractility are discussed as well as the potential importance of the changes in extracellular matrix constituents. The intimal changes induced by hypertension have many similarities to those caused by aging or hypercholesterolemia and can in part reflect general arterial responses to injury. They make the arterial wall more vulnerable to the effects of hypercholesterolemia, however, and as noted in our studies with the Watanabe heritable hyperlipidemic rabbit, pronounced acceleration of atherosclerosis is induced when hypertension is combined with hypercholesterolemia. Antihypertensive drugs can affect the arterial response to hypercholesterolemia. In the present study, new data are provided indicating that captopril inhibits aortic atherosclerosis in the Watanabe heritable hyperlipidemic rabbit in association with a pronounced reduction in cellularity of lesions.