The authors show that thioridazine possesses calcium antagonist activity which may relate to its cardiac and sexual side effects. Binding sites associated with voltage-operated calcium channels were labeled by 3H-nitrendipine. Thioridazine influenced this binding of 3H-nitrendipine in a fashion similar to known calcium antagonists such as verapamil. Thioridazine also antagonized potassium-induced, calcium-dependent contractions of rat vas deferens, with similar potency. Thioridazine concentrations that exert calcium channel antagonist effect correspond to blood levels at therapeutic doses.