The effect of insulin induced hypoglycemia on cerebral energy metabolism was examined in four newborn piglets. Cerebral energy metabolism was assessed using in vivo 31P-nuclear magnetic resonance spectroscopy. It was demonstrated that the normal level of phosphocreatine/inorganic phosphate (PCr/Pi), an indicator of phosphorylation potential, was maintained at a blood glucose level of 40 mg/dL or above, whereas when blood glucose was reduced to less than 40 mg/dL, PCr/Pi rapidly decreased in parallel with this. Below the critical blood glucose level of 40 mg/dL, a positive correlation (y = 0.02x + 0.632; r = 0.668; P < 0.001) existed between blood glucose and PCr/Pi. In the present investigation, a reduction of blood glucose level to 20 mg/dL or lower resulted in a PCr/Pi of less than 1, indicating a state of cerebral energy failure. The intracellular pH (pHi) was 7.08 +/- 0.05 at the onset and 7.15 +/- 0.07 in the hypoglycemic state, indicating no significant difference between the two groups. The present study has clarified that cerebral energy failure occurs when the blood glucose level is about 20 mg/dL or lower. The critical point of blood glucose exists to maintain brain energy metabolism.