Regional blood flow distribution (microspheres) and cardiac output (CO, thermal dilution) were measured during the Cushing response in unblocked (UB), beta-receptor-blocked (BB, 2 mg/kg propranolol iv), or alpha-receptor blocked (AB, 0.5 mg/kg + 0.5 mg X kg-1 X min-1 phentolamine iv) chloralose-anesthetized dogs. Intracranial pressure was increased to 150 mmHg by infusion of temperature-controlled artificial cerebrospinal fluid into the cisterna magna. Similar increases in mean arterial pressure were seen in UB and BB, but in AB a Cushing response could not be sustained. In UB, cerebral blood flow (CBF) decreased 50%, coronary blood flow (CoBF) increased 120%, and peripheral tissue blood flow was reduced only in the kidneys (18%) and the intestines (small 22%, large 35%). Blood flow to the other viscera, skin, and skeletal muscle was unchanged. CO (16%) and heart rate (HR, 38%) decreased, and total peripheral resistance (TPR, 68%) and stroke volume (SV, 38%) increased. In BB, CBF decreased 50%, CoBF decreased 20%, and blood flow was reduced 40-80% in all peripheral tissues. CO (69%) and HR (62%) decreased, TPR increased 366%, and SV was unchanged. We conclude that the Cushing response in UB animals combines an alpha-receptor-mediated vasoconstriction with a beta-receptor cardiac stimulation. The beta-mechanism is neither necessary nor sufficient for the hypertension. However, the combination of alpha- and beta-adrenergic mechanisms maintains cardiac output and peripheral tissue blood flow relatively constant while producing a systemic hypertension.