Cerebrospinal fluid (CSF) electrolyte values have for years been related to levels of central nervous system arousal. Behavioral effects in animals have been shown and theoretically it appears that a variety of drugs, which alter enzyme systems active in the choroid plexus, play a significant part in regulating production of fluid, as well as electrolyte balance in the CSF and ultimately in the extracellular space. The finding of reduced CSF flow and slight reduction of potassium has been confirmed with acetazolamide in children with indwelling intraventricular cannulaeTwenty-three hyperactive children in a state school for the retarded were used as subjects to test out the hypothesis that acetazolamide would reduce hyperactive behavior. For comparison, amphetamine, a commonly used drug in this indication, placebo, and no treatment were used. Activity was measured using a room equipped with monitored toys and sonic sensors as well as global and ward behavior rating scales. Measures of serum and red cell electrolytes were performed. Acetazolamide was found to reduce serum and red cell potassium. No other electrolyte effects were found with any drug. Of the four treatment conditions, acetazolamide and placebo improved hyperactivity; acetazolamide was statistically superiorThe theoretical significance of this finding is not clear, as this drug is known to have many pharmacological actions. Large amounts of the drug enter the CSF and may directly affect neurons; CSF production is reduced and potassium levels are altered; carbonic anhydrase inhibition occurs. Any one of these actions might be relevant, or for that matter, combinations of these effects may account for the undisputable reduction in hyperactivity noted in this short trial