The role of vasopressin, the renin system, and sympathetic activity in sustaining blood pressure in the dehydrated state was investigated in normotensive nonanesthetized male Wistar rats. After 48-h dehydration, plasma arginine vasopressin was 14.0 +/- 1.7 pg/ml and plasma norepinephrine 0.46 +/- 0.05 ng/ml. In another group of rats in which the angiotensin converting enzyme inhibitor (MK 421, 5 mg po twice daily) was administered throughout the dehydration period, blood pressure was reduced by more than 20% (P less than 0.001), and both plasma arginine vasopressin and norepinephrine were higher at 23.4 +/- 3.9 pg/ml (P less than 0.01) and 0.83 +/- 0.07 ng/ml (P less than 0.01), respectively. Taken together, in rats with or without converting enzyme blockade, there was an inverse correlation between mean blood pressure and plasma arginine vasopressin (r = 0.67, P less than 0.01) as well as plasma norepinephrine (r = 0.82, P less than 0.01) levels. The acute administration of a specific vasopressin pressor inhibitor (dPVDAVP) reduced mean blood pressure in the rats with a blocked renin system by 16.9 mmHg (P less than 0.001). In rats without converting enzyme inhibition, the induced fall was only 6.4 mmHg. These results indicate that following 48-h dehydration the renin angiotensin system interacts with the vasopressin secretory mechanism to sustain blood pressure, with renin playing a predominant role. They further suggest that, following blockade of the renin system, activation of the sympathetic nervous system probably also contributes to blood pressure maintenance.