1. The purpose of the experiments was to discover whether the turnover of (22)Na in the c.s.f., which is largely determined by its rate of secretion, is affected in the same manner by inhibitors or accelerators of active transport as the turnover in the brain tissue since there is reason to believe that the composition of the extracellular fluid of brain is controlled by active processes.2. Although acetazolamide (Diamox) inhibits rate of secretion of c.s.f. and the turnover of (22)Na in this fluid it does not appreciably affect the turnover of (22)Na in the brain tissue of either rat or rabbit, the small inhibition observed being probably secondary to the effects on the c.s.f.3. Ouabain inhibits secretion of c.s.f. and turnover of (22)Na in this fluid, but it, also, has no effect on turnover of (22)Na in the brain tissue alone or in combination with Diamox.4. Amphotericin B and amiloride, the anti-aldosterone spirolactone S.C. 114266, all inhibited secretion of c.s.f. without affecting turnover of (22)Na in the brain tissue; actinomycin D, puromycin and cycloheximide, however, had no effect on secretion of c.s.f.5. Vasopressin inhibited secretion of c.s.f. and turnover of (22)Na in this fluid but increased the turnover in the brain by some 16%.6. In the ventriculo-cisternally perfused rabbit, replacement of 80% of the NaCl in the perfusion fluid by choline chloride caused a slowing of the passage of (22)Na from blood into the perfusion fluid.7. On the basis of these results it is concluded that the brain extracellular fluid is not renewed by appreciable bulk-flow, in contrast with the c.s.f.