The cariac response to anesthetic doses of ketamine hydrochloride was studied in dogs, initially in the absence of other drugs and subsequently during beta adrenergic block with propranolol and combined beta adrenergic and cholinergic blockade with propranolol and atropine. Ketamine (4 mg/kg) was injected into the left atrium or the jugular vein. Administration of ketamine alone resulted in increases in heart rate (61 beats/min, P smaller than .001), cardiac output and left ventricular systolic pressure, but left ventricular end-diastolic pressure and dP/dt max (maximum rate of change of left ventricular isovolumic pressure development) were unchanged. After propranolol, the increase in heart rate produced by ketamine was attenuated, and a transient fall in dP/dt max occurred. After propranolol and atropine, heart rate was not changed by ketamine, but dP/dt max fell and left ventricular end-diastolic pressure rose. Systemic vascular resistance was not altered by ketamine. It is concluded that administration of ketamine increases sympathetic discharge and reduces vagal discharge to the heart. In the absence of sympathetic and vegal control over the heart, the drug depresses myocardial contractility.