Sprague-Dawley rats were given treatments, known to decrease 22Na movement into choroid plexus and CSF, to investigate their effect on 22Na transfer across the cerebral capillaries. Acidic salts, acetazolamide, or amiloride was injected intraperitoneally into bilaterally nephrectomized rats, and the rate of 22Na uptake into parietal cortex, pons-medulla, and CSF was determined at 12, 18, and 24 min. Severe acidosis (arterial pH 7.2), produced by HCl injection, decreased the rate of 22Na entry into both brain regions and CSF by 25%, whereas mild acidosis (pH 7.3) from NH4Cl injection reduced brain entry by 18%, but CSF entry by only 10%. Like HCl acidosis, amiloride reduced transport into both brain and CSF by 22%. Penetration of 22Na into parietal cortex was unchanged by acetazolamide, but that into CSF was slowed 30%. Since uptake of 22Na into cortical regions is primarily movement of tracer across the cerebral capillaries when tracer uptake time is less than 30 min, the results indicate that both metabolic acidosis and amiloride decrease Na+ permeativity at the cerebral capillaries as well as at the choroid plexus. Acetazolamide, on the other hand, alters Na+ movement only across the choroidal epithelium.