Cerebral circulatory and metabolic effects of amphetamine sulphate (0.25-25 mg.kg-1 i.v. or 5-10 mg.kg-1 i.p.) were studied in anesthetized, paralyzed and artifically ventilated rats. Cerebral blood flow (CBF) was measured with a modification of the Kety and Schmidt (1948) technique, and oxygen consumption (CMRO2) was calculated from CBF and arteriovenous differences in oxygen content. Regional CBF was evaluated from the uptake of 14C-ethanol. Cortical metabolites were analysed following freezing of tissue in situ. Amphetamine administration gave rise to a marked increase in CBF that was doubled following 0.25 mg.kg-1 and increased 4-fold following 15 mg.kg-1. However, such excessive increases in flow were confined to frontoparietal cortical regions, while other cortical or subcortical areas showed more moderate hyperemia. The increase in CBF was unrelated to changes in arterial PCO2, blood pressure, or tissue lactate content. CMRO2 increased by 30% to 95% depending on dose and rat strain used. At all doses employed, amphetamine gave rise to glycogenolysis in cerebral cortex but, in animals studied within the first 30 min after 5 mg.kg-1, or less, the only other changes were increases in glucose-6-phosphate and alpha-ketoglutarate concentrations. When the dose was increased to 15 mg.kg-1, there were moderate increased in lactate concentration and lactate/pyruvate ratio. Sixty min after 5 mg.kg-1 there were increases in tissue concentrations of pyruvate, citric acid cycle intermediates and alanine, as well.