The role of endothelial cells in modulating the vascular smooth muscle tone in aging and hypertension was examined. Results from in vitro pharmacological studies indicate that vasodilations of rat arteries induced by several dilator agents, such as nitrovasodilators, decrease with advancing age and experimental hypertension. These diminished dilator responses to nitrovasodilators however were not observed in arteries with endothelial cells removed. Furthermore, 8-bromo-cGMP-induced relaxations were not different between arteries with and without endothelial cells and were not affected by hypertension. It appears that the diminished vasodilator responses in aging and hypertension is not initially due to defects in vascular smooth muscle but rather due to an altered modulatory function of the endothelial cells. At different ages and under different pathological conditions, such as hypertension, the ratio of production and/or activities of endothelium-derived relaxing factors and endothelium-derived constrictor factors may vary, and therefore directly or indirectly affect the production of cGMP and smooth muscle tone.