Increased free intracellular calcium ion concentration ([Ca2+]i) has been found in lymphocytes and blood platelets of patients with bipolar affective disorders when they are acutely ill, but not after recovery. Because lithium alters intracellular calcium ion dynamics and lowers platelet [Ca2+]i in affectively ill patients but not controls, drugs whose primary action is to modulate [Ca2+]i in hyperactive cells have been used as antimanic agents. The best studied of these is verapamil, a calcium channel blocking agent (CCB) that appears most effective for lithium-responsive patients. Because they interact with different central CCB receptors, second-generation CCBs may have a different spectrum of action. CCBs are usually well tolerated and may be useful for a number of other psychiatric, neurological and medical conditions.