A radioimmunoassay specific for the N-terminal fragment of prohuman atrial natriuretic factor (hANF) was established with the use of antiserum for pro-hANF (1-30). Plasma levels of alpha-hANF-like immunoreactivity (LI) and pro-hANF (1-30)-Ll in patients with severe hypertension who were receiving a normal sodium diet were 56 +/- 5 pg/ml and 2710 +/- 118 pg/ml, respectively; these levels were significantly higher than control values. Levels of these peptides in patients with mild hypertension were similar to those of control subjects. Mean blood pressure correlated closely with alpha-hANF-Ll levels (r = 0.56, p less than 0.001) and pro-hANF (1-30)-Ll levels (r = 0.66, p less than 0.001) in patients receiving a normal sodium diet. Plasma alpha-hANF-Ll and pro-hANF (1-30)-Ll levels were significantly decreased 3 days in mild hypertension and 7 days in severe hypertension after initiation of a low-sodium diet with a decrease in blood pressure as compared to the initial values. These results suggest that plasma N-terminal fragment levels are elevated in proportion to the degree of hypertension, and they can be reduced by means of effective antihypertensive treatment.