The purpose of the present investigation was to determine whether dexamethasone, an agent known to preserve the blood-brain barrier, and colchicine, an agent that impairs mobilization of macrophages, can prevent demyelinating lesions associated with rapid correction of hyponatremia in the experimental animal. Hyponatremia was induced in rats with Pitressin and water. After 4 days hyponatremic rats received hypertonic saline alone or hypertonic saline plus dexamethasone or colchicine. All of the 9 rats that received only 5% NaCl developed demyelinating disease, while 3 of 6 rats treated with dexamethasone and 5 of 15 rats treated with colchicine showed no CNS abnormality. The results of our investigation might help understand the pathogenetic mechanism of central pontine myelinolysis in humans, a disease attributed to rapid correction of hyponatremia.