After cerebral cortex slices from adult or infant rats had been incubated in medium containing glucose or beta-hydroxybutyrate as an energy source, the concentrations of ATP and amino acids in the tissue and incubation medium were examined. In the adult cerebral cortex, on the substitution of beta-hydroxybutyrate for glucose, the levels of ATP and amino acids were not maintained. The concentrations of glutamate, glutamine and gamma-aminobutyrate decreased, and that of aspartate increased together with the decrease in ATP in the tissue. Similar changes were observed when iodoacetate (10 microM) was added to the incubation medium. Moreover, the depletion of an energy source led to more drastic changes. On the other hand, in the infant cerebral cortex, the substitution of beta-hydroxybutyrate did not affect the levels of ATP and glutamate, glutamine and gamma-aminobutyrate. There are good correlations between the concentrations of ATP and glutamate and related amino acids in the cerebral cortex.