Extensive pharmacological investigations on tetrandrine, one of the traditional medicinal alkaloids, are reviewed. Tetrandrine has been used clinically in China for centuries in the treatment of many diseases. A recent series of studies has revealed major mechanisms underlying its multiple pharmacological and therapeutic actions. One of the most interesting discoveries is that tetrandrine is a new kind blocker of the voltage-activated, L-type Ca2+ channel in a variety of excitable cells, such as cardiac, GH3 anterior pituitary and neuroblastoma cells, as well as in rat neurohypophysial nerve terminals. Although tetrandrine does not belong to any of the three classical Ca2+ channel blocker groups, electrophysiological and radioligand binding studies show that tetrandrine is an L-type Ca2+ channel blocker with its binding site located at the benzothiazepine receptor on the alpha 1-subunit of the channel. In addition, tetrandrine is a blocker of the voltage-dependent T-type Ca2+ channel. It is clear that tetrandrine's actions in the treatment of cardiovascular diseases, including hypertension and supraventricular arrhythmia, are due primarily to its blocking of voltage-activated L-type and T-type Ca2+ channels. Furthermore, this alkaloid is a potent blocker of the Ca(2+)-activated K+ (K(Ca)) channels of neurohypophysial nerve terminals. The blocking kinetics of tetrandrine on the K(Ca) channel is quite different from that of typical K(Ca) channel blockers such as tetraethylammonium and Ba2+. Although the clinical role of tetrandrine as a blocker of the K(Ca) channels is unclear, it is a promising ligand for the study of K(Ca) channel function.