It is well documented that the mature human brain oxidizes only glucose to obtain energy under physiological, nonstarved conditions. Through adulthood to the beginning of senescence, the balance between oxygen and glucose consumption of the brain was found to be unchanged as the basis for energy production. Beyond the age of 70 yr, however, cerebral glucose consumption appears to decrease. In the present study, the effect of advancing age on glucose and energy metabolism in brain cortex of rats was investigated. The study was carried out in male Wistar rats, 6 (young adult), 12 (adult), 24 and 30 (both aged) mth of age. Male Wistar rats may be designated as being 'aged' from 24 mth of life onwards. Intermediates of glycolysis, tricarboxylic acid cycle and energy-rich compounds were measured by means of sensitive standard enzymatic methods under steady-state conditions of arterial normotension, normoxemia, normocapnia and normothermia in anesthesia with 0.5 vol% halothane and nitrous oxide/oxygen 70:30. The 12-mth-old adult rats served as controls. The glucose concentration in brain cortex was found to be about 1.5 times higher in 6-mth-old than in 12-mth-old animals but did not differ in the 12-, 24-, and 30-mth-old rats. Besides glucose, fructose-1,6-phosphate and ATP decreased from young adult to adult rats while pyruvate, malate and creatine phosphate diminish with advancing age. A tendency to reduction with aging was also evident in glucose-6-phosphate, fructose-1, 6-diphosphate, and lactate. The fall in substrate concentrations may be attributed to the reduced activity of enzymes acting in glucose breakdown. It is concluded that glucose and energy metabolism may diminish with the process of normal aging, but that the reduction is of only moderate extent.