The movement of essential substrates from plasma into cerebral structures has been studied in detail in normal alert rats as well as in rats with various metabolic abnormalities. Briefly, radioactive substrates were infused i.v. to rapidly establish and maintain a trace concentration in arterial blood. The rats were killed shortly thereafter, the brain was removed and frozen, and thin sections were cut for quantitative autoradiography. The permeability-to-surface area product (PA) was calculated from the amount of radioactivity accumulated by the brain and the integral of plasma radioactivity. Influx was calculated as the product of PA times plasma substrate concentration. This approach was used to measure the influx of glucose, neutral amino acids, basic amino acids, and ketone bodies. Studies were made of normal rats, rats with portacaval shunts (a model of hepatic encephalopathy), starved rats, diabetic rats, and normal rats infused with ammonium acetate. The results demonstrate specific changes in individual transport systems, which in most cases occurred throughout the brain, although some structures were affected more than others.