An analogue of arginine vasopressin (desmopressin, DDAVP) was evaluated for production chronic hyponatremia and prevention of sickle cell crisis. With sodium restriction (100 meq Na + / day) and water loading ( greater than 3 liters/day), persistent hyponatremia could not be achieved, nor could crises be prevented or aborted. Patients would not comply with a regimen of lower salt and higher fluid intake. More rigorous treatment might be practical during acute sickle cell crises, and a regimen similar to that used here might be more effective in children, whose renal concentrating mechanisms are still intact.