The effects of thiopental on cerebral metabolism were evaluated by means of measurements of cerebral metabolic rate for oxygen (CMRO2) and of tissue levels of organic phosphates, glycolytic substrates, citric acid cycle intermediated and selected amino acids. Shortly after the beginning of thiopental administration, CMRO2 was reduced to half the normal value, and there were signs of retardation of glycolytic flux at the phosphofructokinase step. Inhibition at this regulatory enzymatic step could be related to an increase in phosphocreatine and a fall in inorganic phosphate concentration. The rise in phosphocreatine, and the unchanged levels of ATP, ADP and AMP demonstrate that induction of anaesthesia with thiopental is unrelated to energy failure. Changes in citric acid intermediated included a fall in malate, and probably also in citrate, alpha-ketoglutarate and fumarate, with a tendency towards reduction in the pool of citric acid cycle intermediates; and the amino acid changes were dominated by a progressive rise in aspartate. It is suggested that these changes are secondary to a reduced rate of pyruvate delivery, and to a decrease in malate/oxaloacetate ratio.