The C-terminal fragment of atrial natriuretic factor (ANF) was infused intravenously at 0.5 pmol/kg/min during 12 hours in 6 patients with mild to moderate essential hypertension, and in 6 normotensive volunteers, all recumbent and well hydrated, under a daily intake of 200 and 120 mmoles of sodium and potassium, respectively. Plasma C-terminal ANF tended to increase during ANF and to decrease during vehicle infusions. Plasma concentrations of the N-terminal fragment of ANF decreased by 20 to 40% (p less than 0.05) during ANF and remained unchanged following vehicle infusion, suggesting that exogenous ANF reduces endogenous ANF secretion. ANF increased significantly plasma cyclic guanosine monophosphate (p less than 0.01) from 3.1 +/- 0.4 to 4.3 +/- 0.8 and from 2.8 +/- 0.4 to 5.1 +/- 0.5 nmol/L in controls and patients respectively. ANF reduced systolic diastolic blood pressure during the last 8 hours of the infusion, by about 5% (p = 0.055) in patients, but did not alter blood pressure in controls. Sodium excretion during ANF increased 42% vs vehicle (p less than 0.05), in the patients group and remained unchanged in controls. Hematocrit levels increased significantly in both groups with ANF infusion. We conclude that a prolonged infusion of ANF at a physiological rate causes a modest increase in plasma cyclic guanosine monophosphate, hemoconcentration, and reduces endogenous ANF secretion. It also stimulates diuresis and natriuresis and slightly reduces systolic blood pressure in patients with essential hypertension.