Atrial natriuretic factor (ANF) is the name applied to a family of peptides secreted by the atria, endowed with potent natriuretic, vasorelaxant, and aldosterone inhibitory properties, and which has been purified from animal and human atria. A radioimmunoassay of human plasma ANF was developed. Six normal men, aged between 24 and 38, were studied after 4 days on a low-sodium diet (40 mmol per day) and 4 days on a high-sodium diet (300 mmol per day), in random order. Plasma renin activity was suppressed and plasma aldosterone reduced by the high-sodium diet, as expected. Plasma immunoreactive ANF was 47.9 +/- 4.8 pg/ml on the low-sodium diet and rose to 68.1 +/- 5.9 pg/ml on the high-sodium diet (p less than 0.01). These results demonstrate that secretion of ANF by the heart may be modulated by the changes produced by extreme variations in sodium intake.