Twelve hyponatremic patients with central pontine myelinolysis (CPM) showed a rise in serum sodium levels 3 to 10 days (mean, 6) prior to the development of CPM. The increase exceeded 20 mEq/L within 1 to 3 days and was then sustained for an additional 3 to 5 days. In addition, 11 of the 12 CPM patients achieved a sodium value of 147 mEq/L or greater during the period of sodium elevation. The rise in sodium frequently coincided with administration of saline solutions, diuretics, steroids, and lactulose. In contrast, 9 hyponatremic patients who did not have CPM showed sodium increases that were significantly less or slower (or both) following treatment of hyponatremia. Our findings suggest that CPM may be caused by a too rapid or excessive rise in serum sodium from a hyponatremic baseline.