Synaptosomal glycolysis is stimulated eight- to 10-fold when the respiratory chain is inhibited by cyanide or by anoxia. However, the stimulation is transient and after 15 min declines toward the preanoxic rate. The decline is not seen when Ca2+ is absent or when the respiratory chain is inhibited by rotenone. The decline in glycolysis is reversible, is not due to substrate exhaustion, and is the cause, rather than the effect, of lowered synaptosomal ATP/ADP ratios. The failure to maintain glycolysis when the terminal oxidase of the respiratory chain is inhibited may have relevance to the sensitivity of the brain to anoxic damage.