An exaggerated natriuretic response to volume expansion (VE) is observed in many essential hypertensive patients. The plasma levels of atrial natriuretic peptide (ANP) were measured in 11 normal subjects (NT) and 12 patients with mild essential hypertension (EH) during VE (1 800 ml isotonic saline IV over 3 hours). NT and EH groups were similar with respect to age and basal levels of renin, aldosterone and ANP (34.5 +/- 5.5 in NT and 32.5 +/- 6.3 pg/ml in EH, mean +/- sem). In response to VE, ANP increased to the same extent in both groups (a change of + 19.3 +/- 5.2 in NT and 22.2 +/- 7.1 pg/ml in EH) despite the marked difference in observed natriuresis (36 +/- 3.5 in NT and 54.9 +/- 6.3 mmol/3 in EH, p less than 0.02). The change in ANP induced by VE was inversely correlated with the fall in hematocrit and the variation in fractional excretion of sodium in both groups. These results suggest that atrial natriuretic peptide may participate in the control of the renal response to isotonic volume expansion, but they do not support a predominant role of atrial natriuretic peptide in the exaggerated natriuretic responses to volume expansion of patients with essential hypertension.