Plasma concentrations of immunoreactive (IR)-atrial natriuretic polypeptide (hANP) were measured by radioimmunoassay in 9 essential hypertensive patients after alteration of salt intake and acute saline infusion. Daily salt intake was altered every one week in the order of 15g/day, 3g/day, and 7g/day. On the last day of the first week, 1500 ml of 0.9% saline was infused intravenously over one hour. Plasma concentrations of IR-hANP tended to decrease, although not significant, by salt restriction. Further, there were significant positive correlations between changes in plasma concentrations of IR-hANP and those of several variables such as body weight, systolic blood pressure, and creatinine clearance. Plasma concentrations of IR-hANP rose significantly (p less than 0.05) from 50.7 +/- 20.1 (Mean +/- SEM) pg/ml to 119.0 +/- 48.8 after acute saline infusion. Although there was significant correlation between mean blood pressure and the increase in sodium excretion by saline infusion, this increase was unrelated to the rise in plasma concentrations of IR-hANP. These results suggest that the release of ANP is stimulated mainly by expansion of extracellular fluid volume in hypertensive patients. However, natriuretic and hypotensive effects attributable to the changes of ANP release could not be elucidated.