The acute natriuretic effect of human atrial natriuretic peptide (ANP) has been well described in man. We have now studied possible hormonal mediators of this effect. We studied six healthy volunteers on two occasions when they received either an infusion of ANP of 1.5 pmol X kg-1 X min-1 for 30 min followed by 15 pmol X kg-1 X min-1 for a further 30 min, or matching vehicle infusions in a randomized single-blind fashion. On the placebo day, plasma renin activity (PRA) rose from 1.26 +/- 0.08 to 1.57 +/- 0.14 ng A1 X ml-1 X h-1, while on the ANP study day PRA fell from 1.45 +/- 0.15 to 1.28 +/- 0.05 ng A1 X ml-1 X h-1 (p less than 0.01). No significant changes were found in plasma aldosterone concentrations or in urinary dopamine excretion. These results provide evidence that ANP suppresses renin release in man.