I t is well established that in normal man the renin-angiotensin-aldosterone system is responsive to changes in volume. The present study was performed to determine whether sodium has an action apart from volume in the regulation of the secretion of renin and aldosterone. Acute volume expansion was induced either by saline, dextran, or glucose infusion in supine, normal subjects in balance on a 10 meq sodium/100 meq potassium diet. Plasma renin activity (PRA), angiotensin II (A II), aldosterone (PA), cortisol, serum sodium, and potassium were measured every 10 min for the first 30 min and then at 1, 2, 4, 6, and 8 h.During saline infusion (500 cm³/h for 6 h) mean PRA and A II levels declined very rapidly, falling significantly below control at 10 min (P < 0.01) and by 50% at 60 min. Thereafter, the rate of fall was more gradual, reaching a nadir at 360 min (70-80% below control). PA declined in a parallel pattern except that a significant fall did not occur until 30 min.In contrast to saline, dextran infusion (250 cm³/h for 4 h) did not produce a significant fall in PRA, A II, or PA until 4 h after the start of the infusion despite equivalent volume expansion. On the other hand, the infusion of 5% glucose and water (500 cm³/h for 6 h) did not produce a significant decline in PRA, A II, or PA over the first 6 h of the study. Although the response rate of PRA, A II, and PA was different in each of the three infusion studies, these parameters were significantly correlated within each study. Serum sodium and potassium levels did not change during any study except dextran infusion, where a significant fall in both occurred at 120 min. In all the infusion studies, plasma cortisol levels gradually declined during the 8-h study period consistent with its expected rhythm of diurnal secretion.These results demonstrate that rate of response of the renin-angiotensin-aldosterone system to acute volume expansion with saline differed from that with dextran and glucose infusion in sodium-depleted man. The data support a specific role for volume expansion with saline or the sodium ion per se in the regulation of renin and aldosterone.