To test the hypothesis that hemodilution is a mediator of the renal responses to an isotonic saline infusion in the supine position, eight males underwent 1) intravenous infusion of 1.5 liter of saline over 21 min (Saline), 2) infusion of 1.5 liter of saline in combination with lower body negative pressure for 3 h (LBNP+Saline) to maintain central blood volume unchanged, and 3) a control study without infusion or LBNP. During the Saline series, central venous pressure (CVP) and left atrial diameter (LAD) increased by 4.4 +/- 0.6 mmHg and 2.6 +/- 0.4 mm (P < 0.05), respectively, whereafter they declined toward preinfusion levels. During LBNP+Saline, CVP and LAD were unchanged. Plasma colloid osmotic pressure remained unchanged during control and showed identical decreases by 5 mmHg (P < 0.05) in the Saline and LBNP+Saline series. During the 3rd h of LBNP, renal sodium excretion (U(Na)V) peaked at 296 +/- 55 micromol/min vs. a higher value of 383 +/- 54 micromol/min (P < 0.05) during Saline. The increase in U(Na)V above that of control during the 3rd h of LBNP+Saline constituted 48% of that during Saline. Plasma renin activity and plasma aldosterone concentration showed similar patterns of decrease after saline infusion irrespective of LBNP, whereas plasma norepinephrine was elevated late in the LBNP period compared with during Saline and control (P < 0.05). It is concluded that the maintenance of a constant CVP and LAD reduces the natriuresis of acute saline loading by about one-half. Thus hemodilution in conjunction with suppression of renin and aldosterone release (independent of change in CVP and LAD) might account for the remaining natriuresis of infusion.