1. Total body sodium (TBS) is known as major determinant of arterial blood pressure (ABP) when TBS is increased, but little is known about ABP control following a deficit in TBS. The renin-angiotensin-aldosterone system (RAAS) controls ABP by controlling TBS via the Na-retaining effects of angiotensin (Ang) II and aldosterone, as well as through the vasoconstrictor action of AngII. In the present study, we investigated the role of RAAS elements in ABP control following moderate TBS deficit. 2. Balance studies of 4 days duration were performed in dogs. On Day 1, TBS was reduced by peritoneal dialysis (-3.5 mmol/kg bodyweight). On Days 1 and 2, dogs were on low Na intake (LSI; 0.5 mmol Na/kg bodyweight), whereas on Days 3 and 4 dogs were on high Na intake (HSI; 5.5 mmol Na/kg). In Protocol 1, the RAAS was left intact; in Protocol 2, angiotensin-converting enzyme was inhibited by infusion of the angiotensin-converting enzyme (ACE) inhibitor captopril (7 microg/kg per min) on Days 2-4; and in Protocol 3, in addition to ACE inhibition (ACE-I), mineralocorticoid receptors (MR) were blocked using 300 mg, p.o., spironolactone twice daily on Days 2-4. 3. During LSI, the TBS deficit could not be replenished and osmoregulation resulted in a deficit in total body water (TBW) of -12 to -15 mL/kg bodyweight. The RAAS was massively stimulated. In dogs with an intact RAAS, ABP did not decrease despite the TBW deficit. This was achieved by the vasoconstrictor action of AngII. At the same TBW deficit, ACE-I significantly lowered ABP by approximately 17 mmHg. In dogs with an intact RAAS, the deficit in TBS and TBW was immediately replenished when enough Na was offered (HSI). Even during ACE-I, the deficit was almost replenished. This was accomplished by AngII-independent stimulation of aldosterone release. Arterial blood pressure increased in parallel with TBW. With additional blockade of MR, the deficit was not replenished and ABP remained reduced. 4. These results indicate that with a moderate deficit in TBS and TBW, the RAAS is the major factor controlling ABP. First, the vasoconstrictive action of AngII fully compensates for the volume deficit. Second, stimulation of both renin release (and, thus, AngII and aldosterone) and aldosterone release independent of AngII is crucial for the restoration of TBS and TBW, thus controlling ABP.