Background B-type natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) are secreted from the heart and are thought to be equally important factors in the regulation of vascular tone in health and in congestive heart failure (CHF). However, no studies directly compare vasodilator effects of these peptides in healthy subjects and in patients with CHF. Methods Plethysmography was used to determine the vasodilatory effects of BNP and to compare these to the effects of ANP in patients with CHF (n = 15) and age-matched healthy subjects (n = 16). Graded doses of ANP and BNP (8, 16, 32, and 48 pmol/min per 100 ml of tissue volume for both) were administered randomly into the brachial artery. Forearm blood flow (FBF) was measured, and cyclic GMP (cGMP) spillover was calculated. Results Responses in FBF to both peptides in CHF were significantly lower than those of healthy subjects (BNP p < 0.05; ANP p < 0.01). Similarly, forearm spillover of cGMP was significantly lower in CHF than in healthy subjects (BNP p < 0.05; ANP p < 0.01). When vascular responses in healthy subjects were compared between BNP and ANP, BNP-induced changes in FBF (p < 0.05) and forearm cGMP spillover (p < 0.01) were significantly less than changes induced by ANP. In CHF, though, FBF change and cGMP spillover induced by the two peptides were not significantly different. Conclusions These results suggest that the metabolism and action of these natriuretic peptides in CHF may differ from the healthy state. (Am Heart J 1998;135:414-20.)