Voltage-dependent calcium channels are crucially important for calcium influx and the following smooth muscle contraction. β subunits of these channels are known to modify calcium currents through pore-forming α 1 subunits. Among the four reported independent β subunits, the β3 subunit is expressed in smooth muscle cells and thought to compose L-type calcium channels in the tissue. To determine the role of the β3 subunit in the cardiovascular system, we have analyzed β3-null mice. Electrophysiological examinations proved the existence of dihydropyridine (DHP)-sensitive, L-type calcium channels in the smooth muscle cells. β3-null mice show no apparent changes in smooth muscle contraction and sensitivity to DHP, and normal blood pressure when they are raised on a normal diet, but the β3 subunit deficient mice show elevated blood pressure in response to a high-salt diet, with significant reductions in plasma catecholamine concentrations. Our finding strongly suggests a close relationship between voltage-dependent channels and high blood pressure.