Synthetic atrial natriuretic factor (ANF) has been found to be a potent relaxant of isolated vascular preparations. ANF is more effective in relaxing agonist-induced versus depolarized contractile events and the relaxation efficacy appears inversely related to the level of contractile preload. The vasorelaxation to ANF is associated with elevations of cyclic GMP via an activation of the particulate form of guanylate cyclase. Both species and regional-vascular differences exist, in vitro as well as in vivo, in the vasorelaxation response to ANF which may reflect an altered distribution of high affinity receptors and/or different states of active vascular tone of the particular preparation.