The permeability of the blood-brain barrier to ketone bodies, substrates of the monocarboxylic acid carrier, was measured in individual brain structures of control and portacaval-shunted rats. The measurements were made 5-7 wk after the shunt or sham operation by quantitative autoradiography. Portacaval shunting caused the permeability to ketone bodies to decrease throughout the brain by approximately 70%. There was a striking change in the transport pattern in the cerebral cortex; deeper cortical layers were affected more than superficial layers. Ketone body consumption by brain is limited by the transport capacity of the monocarboxylic acid system. Therefore, in portacaval-shunted rats the very low activity of this system makes it unlikely that ketone bodies can make a substantial contribution during situations such as fasting. Likewise, other substrates of the monocarboxylic acid system, e.g., lactate and pyruvate, will have greatly restricted access to the brain after portacaval shunting. If the carrier is symmetrical, another consequence will be that exit of endogenously produced lactate will be retarded.