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1. The regulation of cerebrospinal fluid (c.s.f.) bicarbonate concentration was studied using the cat choroid plexus isolated in a chamber in situ. 2. Decreases in plasma bicarbonate concentration caused relatively small changes in the c.s.f. bicarbonate concentration. 3. Alterations in c.s.f. bicarbonate concentration (c.s.f. HCO3-=9 or 28 m-equiv/l.) were countered by changes in the bicarbonate concentration of the fluid produced by the plexus or in the rate of bicarbonate transport which returned c.s.f. bicarbonate towards normal. 4. There was significant regulation of pH in the choroid plexus fluid during hypocapnia and hypercapnia. 5. Alterations of plasma acid-base status did not significantly alter the potential difference across the choroid plexus. However, the potential difference increased when c.s.f. bicarbonate was increased and decreased when c.s.f. bicarbonate was decreased. 6. The data indicate that the bicarbonate concentration in the c.s.f. is actively regulated by the choroid plexus during acid-base disturbances occurring either systemically or in the c.s.f.