The effects of hypercapnia (PaCO2 80, 160 and 300 torr) on cerebral metabolic rate for oxygen (CMRO2) and blood flow (CBF) were evaluated in paralyzed, mechanically ventilated rats by use of a 133Xe modification of the Kety-Schmidt inert-gas technique. Hypercapnic rats (PaCO, 80 torr) maintained on N2O, 70 per cent, had a sixfold increase in CBF and a 25 per cent increase in CMRO2, which were not prevented by adrenalectomy or decreases in tissue O2 tensions to near-normal values. Further increases in arterial blood CO2 tensions were associated with decreases in CMRO2 to normal (PaCO2 160 torr) or subnormal values (PaCO2 300 torr). In the last situation there was only a threefold increase in CBF. In rats with PaCO2 about 80 torr that were given propranolol, 2.5 mgċkg-1, during N2O anesthesia, there was only a threefold increase in CBF, while CMRO2 decreased to below normocapnic control values. Rats with PaCO2 80 torr given sedative or anesthetic doses of diazepam (ventilated with O2, 30 per cent, in N2) also had decreased CMRO2 values and had a twofold increase in CBF. It is concluded that hypercapnia activates catecholaminergic neurons in the brain, and that this activation increases oxygen consumption. The increase in flow that occurs with hypercapnia is markedly influenced by activity in catecholaminergic neurons.