The pharmacological activities of synthetic mammalian brain natriuretic peptides (BNP) from the human, pig and rat were examined in rats. These peptides all elicited diuresis and hypotension, relaxed isolated rat aorta, augmented cyclic GMP concentration in cultured rat vascular smooth muscle cells, and bound to the cells with a high affinity. Pig and rat BNPs were as active as atrial natriuretic peptides from the human and the rat (alpha-hANP and alpha-rANP) for the diuretic and hypotensive effects as well as for cyclic GMP augmentation, while human BNP was about 10 times less potent. Rat BNP was not as active as the other peptides in competing with the binding of [125I]alpha-hANP to rat vascular smooth muscle cells. Thus, the BNPs did not have identical pharmacological profiles although the potencies of the peptides for cyclic GMP augmentation correlated well to those for vasorelaxation.