The interaction between atrial natriuretic peptide (ANP) and the renin-angiotensin-aldosterone (RAA) system was studied in 6 healthy volunteers using the angiotensin-converting-enzyme (ACE) inhibitor, captopril. Each volunteer received, on separate occasions in random order, 48 hours treatment with a) low-dose captopril (6.25 mg twice daily), b) 'high-dose' captopril (25 mg twice daily) and c) placebo prior to an infusion of synthetic human ANP (99-126). Resting plasma ANP levels were significantly (P less than 0.01) higher on treatment with 'high-dose' captopril when compared with low-dose captopril or placebo. 'High-dose' captopril reduced mean arterial blood pressure (BP) and significantly (P less than 0.01) reduced the natriuretic response to the human ANP infusion. These results support the hypothesis that ACE is involved in ANP metabolism. The reduced renal response to ANP during treatment with captopril may reflect the dependence of ANP on adequate renal perfusion pressure and angiotensin II levels to exert its natriuretic effect.