The goals of the present study were twofold: first, to assess the renal excretory and hormonal responses to chronic water restriction in dogs whose sodium retaining mechanisms had been stimulated through dietary sodium (Na+) deprivation; second, to determine the mediator(s) of the natriuresis which was observed with water restriction in these sodium deprived dogs. Three groups of dogs maintained on a low Na+ diet (5 mEq/day) for two weeks underwent a three day period of water restriction. In normal, intact dogs Group 1 (N = 5), water restriction resulted in a significant increase in Na+ excretion with a net cumulative loss of 26.3 +/- 2.6 mEq over three days. The natriuresis was associated with a significant increase in plasma vasopressin (PAVP) (1.7 to 10.2 pg/mliter) and a significant fall in plasma aldosterone (PALDO) from the levels observed with Na+ restriction alone (24.9 to 12.4 ng/dliter). The natriuresis could not be explained by decreases in food intake as determined by control studies in four dogs. Group 2 (N = 6) dogs had a decrease in PALDO with water restriction that was prevented by means of continuous i.v. aldosterone infusion (6.0 micrograms/kg/day). Dogs in this group failed to demonstrate a natriuresis during three days of water restriction, despite the fact that PAVP rose from 3.3 +/- 0.8 to a peak level of 14.95 +/- 1.9 pg/mliter. Group 3 (N = 6) dogs underwent selective neurohypophysectomy, thus preventing the rise in PAVP during three days of water restriction. In this group, PALDO also remained unchanged from the Na+ deprived level during water restriction, and no natriuresis was observed. We conclude: 1) that the natriuresis which occurs with water restriction is a potent physiological response that occurs even in the Na+ restricted state; and 2) this natriuresis can be explained by a fall in PALDO and not the rise in PAVP.