The mechanism by which exogenous calcium reduces blood pressure was investigated. The verapamil (300 micrograms/kg i.v.)-induced decrease of the mean arterial pressure in the conscious rat was prolonged by 400% by pretreatment with CaCl2 (300 mumol/kg i.v.). This ability of calcium to enhance the effect of verapamil was decreased by i.c.v. injection of EDTA (10 nmol/kg). In light of our previous reports, these results suggest that i.v. calcium reduces blood pressure by a central calcium-calmodulin-dependent mechanism.