The hemodynamic responses to i.v. infusion of 0.3 and 0.6 microgram/kg per min of human atrial natriuretic factor (hANF [102-126]) in intact, conscious, one-kidney, perinephritic, hypertensive beagles were examined and compared with the responses in ganglionic-blocked dogs. Blood pressure and heart rate were not affected but plasma ANF-like immunoreactivity was increased by as much as 627%. After hexamethonium (20 mg/kg, i.v.) blockade, a dose-dependent hypotensive response of up to 29 mmHg with no change in heart rate was observed. It is concluded that the compensatory mechanisms of the neurally mediated baroreflex system masked the depressor actions of hANF.