Previous studies from this laboratory have demonstrated that the redistribution of blood volume and concomitant central hypervolemia induced by water immersion to the neck (NI), produces a prompt and profound suppression of plasma renin activity (PRA) and plasma aldosterone concentration (PA) without concomitant alterations in serum sodium and potassium concentrations. The NI model was utilized to assess the responsiveness of PA to volume expansion in 12 anephric subjects. The patients were studied on 2 occasions, 48 h after their last dialysis: during a seated control study (7 of the patients) and during 3 h of NI (all 12 patients). The conditions of seated posture and time of day were identical. Blood for PRA, PA, and cortisol was obtained at 30-min intervals for 5 h. PRA was undetectable in all patients. NI failed to alter PA. Plasma cortisol declined progressively throughout NI; serum potassium concentration remained unchanged. An identical NI study in normal subjects suppressed PA by 60%. These data demonstrate that when plasma composition and posture are maintained constant, marked central hypervolemia does not alter PA in anephric man. The present findings support the role of the renin-angiotensin system as the prepotent mediator of volume-induced changes in PA.