We have studied the hemodynamic and hormonal effects of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in eight patients with cor pulmonale, Subjects were studied twice and were given a 20-min placebo infusion followed by either ANP or BNP (3 pmol/kg/min then 10 pmol/kg/min for 20 min each), Responses were measured after placebo infusion and following low-dose then high-dose ANP or BNP. Placebo infusion had no significant effects on either study day. Low-dose ANP and BNP significantly reduced mean pulmonary artery pressure (MPAP) from baseline by 3.7 mm Hg (95% confidence interval [CI], 1.4 to 6.1) and 3.0 mm Hg (95% CI, 0.6 to 5.4), respectively. High-close ANP and BNP further reduced MPAP from baseline by 7.1 mm Hg (95% CI, 4.8 to 9.4) and 7.1 mm Hg (95% CI, 4.7 to 9.6), respectively. Effects on total pulmonary vascular resistance were similar, ANP and BNP had no confounding systemic hemodynamic effects. Plasma aldosterone was significantly suppressed from baseline by ANP: 156 pmol/L (95% CI, 93 to 220) after low dose, 275 pmol/L (95% CI, 207 to 343) after high dose; and by BNP: 92 pmol/L (95% CI, 30 to 153) after low dose, 159 pmol/L (95% CI, 93 to 220) after high dose. ANP and BNP produced dose-related pulmonary vasodilatation in patients with cor pulmonale, without worsening oxygen saturation or affecting systemic hemodynamics. ANP and BNP also exerted favorable neurohormonal effects by suppressing aldosterone.