The ability of unanesthetized, long-term hypophysectomized (HPX) rats to excrete a saline challenge was evaluated. HPX rats were hypophysectomized 1-2 months prior to experiments. Saline was administered either by intragastric gavage or by intravenous infusion. For 3 hr following gastric saline loading, HPX rats excreted significantly less sodium and potassium than did intact rats. When saline was administered intravenously, both intact and HPX rats excreted similar amounts of sodium during 3 hr of continued volume expansion. On the other hand, potassium excretion was again markedly lower in saline expanded HPX rats than in intact rats. Saline expanded HPX rats in both series of studies had lower excretion rates of creatinine and had lower plasma aldosterone and corticosterone concentrations than expanded intact rats. Urine osmolalities were not significantly different between intact and HPX rats, either before or after volume expansion, indicating that there was at least partial recovery of posterior pituitary function in the HPX animals. These results suggest that adequate anterior pituitary function is required for supporting the kaliuresis but not the natriuresis associated with saline expansion.