An acute increase in plasma tonicity results in an adaptive increase in brain organic osmolyte content, but this process requires several days to occur. Slow reaccumulation of brain organic osmolytes may contribute to osmotic demyelination. It was investigated whether administration of intravenous myoinositol in rats could speed entry of the osmolyte into the brain. Two groups of animals were studied: normonatremic animals and animals with hyponatremia (105 mmol/L) of 3-d duration. Animals were intravenously administered either 1 M NaCl to induce a 25 to 28 mM increase in serum sodium concentration over 200 min or an infusate that maintained serum sodium concentration. In some animals, myoinositol was administered intravenously over the same time period to raise plasma myoinositol levels by 5 to 10 mM. Brain myoinositol, electrolyte, and water contents were determined at the end of the infusions. In both normonatremic and hyponatremic rats, infusion of hypertonic saline without myoinositol or infusion of myoinositol without hypertonic saline did not increase brain myoinositol levels above control levels. In normonatremic animals, concurrent infusion of hypertonic saline and myoinositol increased brain myoinositol levels by about 50% above control levels. Brain myoinositol content in animals with uncorrected hyponatremia was about 50% of that found in normonatremic controls; concurrent infusion of hypertonic saline and myoinositol increased brain myoinositol to levels similar to those found in normonatremic controls. Intravenous infusion of myoinositol did not alter brain water content compared with animals not infused with myoinositol. In conclusion, systemic infusion of myoinositol can rapidly increase brain myoinositol content, but only when plasma tonicity is concomitantly increased.