In patients with essential hypertension and healthy controls, plasma levels of atrial natriuretic peptide (ANP), angiotensin II (Ang II), aldosterone (Aldo), arginine vasopressin (AVP) and urinary excretion of prostaglandin E2 (PGE2) were measured under basal conditions, and before and after acute volume expansion with a 2.5% hypertonic sodium chloride solution. Tubular sodium handling was assessed by the lithium clearance technique. Under basal conditions ANP was increased in patients compared with controls (9.0 pmol/l versus 7.5 pmol/l, P less than 0.01). In response to acute volume expansion patients exhibited exaggerated increases in ANP (5.3 pmol/l versus 3.0 pmol/l, P less than 0.05), exaggerated natriuresis, and an abnormal decrease in fractional proximal and distal tubular sodium reabsorption (PFRNa and DFRNa, respectively). Furthermore, during comparable urinary flow rates, urinary PGE2 excretion was decreased in patients compared with controls (266 pg/min versus 705 pg/min, P less than 0.05). No differences were found between patients and controls in Ang II, Aldo or AVP under basal conditions. Both groups responded to hypertonic acute volume expansion with comparable decreases in Ang II and Aldo, and an increase in AVP. It is concluded that in essential hypertension ANP is increased under basal conditions and the increase in natriuresis and ANP is exaggerated during acute volume expansion. The exaggerated natriuretic response to acute volume expansion resulted from an altered handling of sodium in both proximal and distal tubules.