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1. The effect of marked hypercapnia (arterial PCO2 100 mmHg), nonrespiratory acidosis (pH 6-95-7-15) or hypoxia (arterial PO2 10-15 mmHg) upon penetration of labelled sucrose from blood into brain and c.s.f. has been investigated in exteriorized foetal sheep and new-born lambs. 2. In hypercapnia there was a consistent increase in c.s.f./plasma sucrose ratio after 90 min I.V. sucrose to four to five times control. Brain/plasma sucrose ratios were more variable. Usually there was an increase (up to three-and-a-half-times control); sometimes there was no change or even a decrease. The effect of hypercapnia on sucrose penetration was reversible. 3. Hypercapnia reduced c.s.f. secretion rate to approximately half the control value. Hypercapnia also caused a decrease in brain extracellular space. 4. Non-respiratory acidosis did not affect sucrose penetration. Hypoxia caused a decrease in brain/plasma sucrose ratio. 5. It is concluded that hypercapnia can cuase an increase in cerebral vascular permeability to sucrose in foetal and new-born sheep. Some possible mechanisms are discussed.

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