We investigated sodium and volume-dependent mechanisms in the modulation of adrenal and renal vascular responsiveness to angiotensin II in hypertensive (n = 9) and normal subjects (n = 5) who demonstrated normal responses during steady-state salt balance (intact modulation). Adrenal and renal vascular responses to angiotensin II were assessed on four occasions. These studies were performed during steady-state high salt and low salt balance and later during non-steady state conditions, after acute volume expansion with normal saline or dextran infusions. The volume expansion studies were administered while study subjects were in low salt balance. In both the normal and hypertensive patients saline and dextran suppressed plasma renin activity and aldosterone release, induced renal vasodilation and enhanced the renal vascular response to angiotensin II, similar to that observed during high salt balance. Saline also reduced the adrenal response to angiotensin II in normal subjects but the adrenal response to angiotensin II in hypertensives remained enhanced. The slopes of regression lines relating angiotensin II and aldosterone following saline infusion were significantly different (P < 0.05) between normal subjects (21 +/- 6) and hypertensives (110 +/- 33). Volume expansion with dextran did not effect the normal or hypertensive adrenal response to angiotensin II. We have demonstrated that the renal vascular response to angiotensin II is rapidly modulated by volume expansion per se in normal subjects and hypertensive patients with intact steady-state renin-angiotensin-aldosterone system responses. However, hypertensives have a delay in resetting the adrenal responsiveness to angiotensin II suggesting that they have altered sodium perception during rapid changes in salt balance.