The purpose of these experiments was to study the effects of acetazolamide, a carbonic anhydrase inhibitor, on cisternal cerebrospinal fluid (CSF) ions during normal acid-base balance. We measured blood and CSF acid-base variables in two groups (n = 6 in each) of anesthetized, paralyzed and mechanically ventilated dogs with bilateral ligation of renal pedicles. After baseline samples were obtained, acetazolamide was administered intravenously within 10 min (group II); group I received equal volume (20 ml) of half-normal saline. During the next 6 h, in both groups arterial blood acid-base variables and plasma strong ions remained relatively normal. In group I, mean values for cisternal CSF PCO2 were 45.3 and 49.3 mm Hg at 0 and 6 h; respective values for CSF [HCO-3] were 24.1 and 22.7 mEq/L. In group II, corresponding values for PCO2 and [HCO-3] were 46.4 and 51.9 mm Hg, and 23.8 and 23.7 mEq/L, respectively. Comparing the two groups, related mean values were not significantly different from each other. Furthermore, acetazolamide had no significant effect on CSF Na+, K+ and Cl- concentrations. Based on the results of this study and those reported previously, we conclude that under normal acid-base balance, acetazolamide does not change ionic composition of cisternal CSF, choroidal CSF or brain extracellular fluid.