Chronic sodium depletion is a state of reduced cardiac output in which the renin-angiotensin system is actively involved in maintenance of mean arterial blood pressure (MAP). Angiotensin II (ANG II) blockade with saralasin is known to produce renal vasodilation and a decrease in MAP in the sodium-deplete dog. In this study conscious trained dogs with chronic indwelling catheters were sodium depleted with diuretics plus a low sodium diet. Hepatic blood flow (HBF) and renal blood flow (RBF) were determined concurrently by the clearances of bromosulfophthalein and p-aminohippurate, respectively. When compared with the sodium-repleted state, the depleted dogs had reduced HBF with no change in MAP or RBF. In addition, the hepatic renin clearance and percent hepatic renin extraction were reduced. When saralasin was given intravenously to the depleted dogs, the response was a decrease in MAP with a concurrent decrease in both renal and splanchnic vascular resistances. The increased plasma renin activity during saralasin was accompanied by increased hepatic renin extraction but no significant rise in hepatic renin clearance. Saralasin also resulted in a large decrease in the urinary excretion of prostaglandin E2. This study provides evidence that increased plasma ANG II levels are responsible for the increased splanchnic vascular resistance during chronic sodium depletion.