Effects of diltiazem, a calcium antagonist, on the cardiovascular system in the pentobarbital anesthetized dogs were investigated. Diltiazem (100 micrograms/kg and 300 micrograms/kg, i.v.) decreased blood pressure, heart rate and total peripheral resistance, while cardiac output and stroke volume were markedly increased. The max dp/dt of left ventricular pressure tended to increase with a dose of 100 micrograms/kg. Left ventricular end-diastolic pressure was slightly increased with a dose of 400 micrograms/kg. Rate pressure product was significantly reduced. Diltiazem (30 micrograms/kg and 100 micrograms/kg) increased pulmonary arterial flow together with the increase in both systolic and diastolic pulmonary arterial pressure. Diltiazem (100 micrograms/kg) increased common carotid, femoral and superior mesenteric arterial blood flow by 30 to 40%, whereas vertebral blood flow was increased by over 100%. The dose dependency in the vertebral blood flow was remarkable. Response of the vertebral artery to diltiazem was similar to that reported in the case of the coronary artery. In the His bundle electrogram, diltiazem increased the AH interval by about 10% at 100 micrograms/kg and 25% at 200 micrograms/kg, without changing the HV interval. Diltiazem-induced AH prolongation was completely depressed by epinephrine but only partially so by CaCl2. Thus, the effects of diltiazem on sinus rhythm and AV conduction in the anesthetized dog were more potent than the effects on cardiac contractility, although weaker than the effects of the vasodilating action. The vasodilator effects appear to be the primary action of diltiazem on the cardiovascular system.