Elevated vascular resistance is the key factor in most cases of essential hypertension. Vascular resistance is determined by the sarcoplasmatic concentration of free Ca2+. Experimental studies have shown an increased dependence for the noradrenaline-induced contraction on extracellular Ca2+ from the aorta to the small resistance vessels. This is in accordance with the potent vasodilating effect found with Ca2+-influx inhibitors in man. Furthermore, a selective enhancement of the vasodilating response to verapamil has been found in patients with essential hypertension as compared to normotensive subjects. The verapamil-induced vasodilation in the hypertensive patients was positively correlated to plasma adrenaline concentration. These findings suggest accentuated Ca2+-influx dependent vasoconstriction in essential hypertension, which is related to the activity of the sympathetic nervous system. Acute administration of verapamil and nifedipine results in a distinct fall in blood pressure in patients with essential hypertension but not in normotensive subjects. Generally, the percentage fall in blood pressure with Ca2+-channel blockers has been closely positively correlated to the initial blood pressure level and in an open study with 43 patients with essential hypertension the decrease in blood pressure to verapamil was also positively correlated to the age of patients. These data may provide the basis for a new treatment concept for essential hypertension proposing a Ca2+-channel blocker as the first choice for the older patients and a beta-adrenoceptor blocking agent as the first line drug for the younger patients. Combined treatment with a beta-adrenoceptor blocking agent and a Ca2+-channel blocker seems most efficient in normalizing blood pressure in many therapy-resistant hypertensive patients.