When chronic hyponatremia is rapidly corrected, reaccumulation of brain organic osmolytes is delayed and brain cell shrinkage occurs, leading to the osmotic demyelination syndrome (ODS). We hypothesized that treatment with myoinositol, a major organic osmolyte, could prevent ODS. Severe hyponatremia was induced in adult male rats by administration of arginine vasopressin and intravenous infusion of dextrose and water. Sixty-four hours after induction of hyponatremia, all animals underwent rapid correction of hyponatremia with infusion of hypertonic saline over 4 hours, increasing the serum sodium from 105 to 135 mM; half of the animals were also given myoinositol intravenously beginning 20 minutes before correction and continuing for 28 hours. Serum sodium concentrations were equivalent in both groups at all time points. At 7 days, 7 of 8 animals that received myoinositol survived compared with one of the 9 control animals (p < 0.01). In a second study, sodium was reduced to 106 mM over 64 hours in 24 animals and then corrected by 20 mM over 4 hours with concomitant loading and infusion of either mannitol (control) or myoinositol. Animals were killed 96 hours after correction of hyponatremia was begun. Myoinositol-treated animals had significantly fewer demyelinating lesions than mannitol (2.25 +/- 1.1 versus 6.42 +/- 1.4 lesions/brain, p < 0.03). We conclude that myoinositol administration improves survival and reduces myelinolysis after rapid correction of chronic hyponatremia in rats.