Rats were infused with a selective agonist of vasopressin V2 receptors (1-desamino-D-arginine vasopressin; DDAVP) at two different doses (1 or 5 ng/h) and fed a liquid formula to produce both moderate (plasma [Na+] = 119-124 mmol/l) and severe (plasma [Na+] = 106-112 mmol/l) hyponatremia. Whole body water and electrolyte contents were analyzed after 1, 7, and 14 days of hyponatremia to assess the relative contributions from water retention and sodium depletion to hyponatremia of varying duration and severity. Body water of the hyponatremic rats was significantly increased over normonatremic control rats after 1 and 7 days; after 14 days, the 1 ng/h DDAVP-infused rats also had elevated body water, but the 5 ng/h DDAVP-infused rats returned to levels not significantly different from controls. Body Na+ and Cl- both decreased significantly after 1 day of hyponatremia, and these decreases were sustained for 14 days; measured decreases were significantly greater in the more hyponatremic rats compared with the less hyponatremic rats. Body K+ of the 1 ng/h DDAVP-infused rats was not different from control rats, but significant K+ decreases occurred in the 5 ng/h DDAVP-infused rats after 7 and 14 days. Analysis of the measured plasma Na+ concentrations vs. those predicted by the changes in body water and sodium showed that both water retention and sodium losses were necessary to predict the final plasma [Na+]. However, the relative contribution from each varied with the duration of induced hyponatremia: acutely, water retention was the major cause of decreased plasma [Na+], but sodium depletion became predominant with longer periods of sustained hyponatremia.