We studied the fluid and electrolyte response of the brain and cerebrospinal fluid (CSF) in the lightly anesthetized newborn puppy exposed to acute (1-3 h) mild hyponatremia (12% decrease) and hypernatremia (7% increase). The changes in CSF osmolality, sodium, and chloride were equal to those in plasma. Blood acid-base values and CSF PCO2 remained normal, but in CSF there was a transient dilution acidosis in hyponatremia and contraction alkalosis in hypernatremia. In brain tissue, with hyponatremia, brain water increased in proportion to the osmotic stress (a change which was greater than that previously observed in adults) and the chloride space increased in the puppy (a change that was opposite to that observed in adults). There were no significant changes in dry tissue potassium, sodium, or chloride content. In hypernatremia, brain water decreased less than predicted by the osmotic change, the chloride space was unchanged, dry tissue potassium and chloride increased, and sodium was unchanged. In the newborn puppy, brain cell and extracellular volume regulation is not apparent with acute hyponatremia but is with hypernatremia.