AbstractBrain cortex slices from fed, 48 h and 120 h fasted rats were incubated and14CO2was measured from (a) [U‐14C]glucose (5 mm) either alone or in the presence ofl‐lcucine (0.1 or 1 mm), and (b) [U‐14C]leucine or [l‐14C]leucine at 0.1 or 1 mmwith or without glucose (5 mm). In other experiments, sodiumdl‐3‐hydroxybutyrate (3‐OHB) or acetoacetate (AcAc) at 1 or 5 mmwere added in the above incubation mixture. The rate of conversion of [U14C]glucose to CO2was decreased 20% by leucine at 1 mmand 30–50% by 3‐OHB at 1 or 5 mmbut not by leucine at 0.1 mm. The effects of 3‐OHB and of leucine (1 mm) were not additive. The effects of leucine were similar in the fed and fasted rats. The rate of conversion of [U‐14C]leucine or [l‐,4C]leucine to14CO2at 0.1 mmand 1.0 mmwas increased by glucose (35%) in the fed or fasted rats. Ketone bodies in the absence of glucose had no effect on leucine oxidation. However, the stimulatory effect of glucose on the rate of conversion of leucine to CO2was inhibited by 3‐OHB at 5 mm. These results suggest that (a) leucine in increased concentrations (1 mm) may reduce glucose oxidation by brain cortex while itself becoming an oxidative fuel for brain, and (b) leucine oxidation by brain may be influenced by the prevailing glucose