✓ The relationship among cerebral blood flow (CBF), blood volume, cardiac output (CO), and mean arterial blood pressure (MABP) at varying levels of arterial CO2 tensions (PaCO2) were studied in 70 normal cats. The CBF was measured from the clearance curve of xenon−133 and CO with a thermal dilution catheter placed in the pulmonary artery. The CBF, CO, and MABP values varied appropriately with changes in PaCO2, confirming the reliability of the preparations and the presence of normal autoregulatory responses. Moderate hypovolemia that did not change MABP did, nevertheless, significantly decrease CO and CBF. In an effort to determine if this decrease in CO and CBF were coupled responses, the effects of beta stimulation, hypervolemia, and alpha and beta blockade were investigated. Propranolol, in a dosage insufficient to change MABP, decreased both CO and CBF. This agent abolished the CO response to elevations in PaCO2 but not the CBF response, making it unlikely that this CBF reduction resulted from impaired cerebral autoregulation. Isoproterenol, which, in contrast to propranolol, does not cross the normal blood-brain barrier, alone or in combination with phenoxybenzamine, produced a 38% and 72% increase in CO, respectively, without a change in CBF. Alpha blockade (no major change in CO) and beta blockade (major decrease in CO) did not significantly effect cerebral autoregulation to changes in MABP from angiotensin. The ability of the brain to resist increases in MABP and CO and maintain normal CBF is explained by normal cerebral autoregulation. However, its vulnerability to modest decreases in blood volume, which cannot be attributed to variations in perfusion pressure, is unexplained but obviously has important therapeutic implications. This may be related to reduction in CO, changes in autonomic activity, or a decrease in the size of the perfused capillary bed.