This study examines whether an increase in renal perfusion pressure (RPP) is necessary to escape endogenously stimulated Na- and water-retaining mechanisms. In seven dogs stimulation was accomplished by a servo-controlled reduction of RPP (rRPP) below the threshold for pressure-dependent renin release for 4 days. Oral intake was standardized. Plasma renin activity (PRA) rose from 2.5 in controls to approximately 5 ng ANG I.ml-1 x h-1 during rRPP days. Plasma aldosterone concentration (PAC) increased by approximately 50% only on day 1 of rRPP but fell at or below control levels thereafter. The PAC-to-PRA ratio decreased during rRPP days. Atrial natriuretic factor (ANF) rose to values three times higher than in controls. Mean systemic blood pressure (MABP) rose from 111 +/- 12 in controls to 142 +/- 14 mmHg on day 4 of rRPP. On day 1 of rRPP 60% of the Na and 24% of the water intake were retained. However, after 2-3 days the input-output balance was restored but on a higher level of total body Na and total body water (new "set point"). Because elevated systemic MABP could not exert direct pressure effects on the kidneys due to servo control of rRPP, there must be other factors, e.g., fall in PAC, increase in ANF, and changes in intrarenal hemodynamics and physical factors that may have contributed to the resetting of input-output balances during rRPP.