The vasodilator profile of synthetic atrial natriuretic factor (ANF) was characterized using isolated vascular preparations. Nanomolar concentrations of ANF relaxed rabbit aortic rings contracted by serotonin, histamine, methoxamine or angiotensin II. The synthetic peptide was most effective (IC50 = 1.3 X 10(-10) M) in relaxing the tonic, intrinsic contractions of the rabbit facial vein. ANF was poorly active against K+-contracted aortic rings or the phasic contractions of the rat portal vein. A similar vasodilator profile was obtained for sodium nitroprusside but not papaverine, hydralazine, adenosine or nifedipine. This first demonstration of the vascular activity of synthetic ANF depicts this substance as a nonselective vasodilator of agonist-induced contractions. The observed similarities in the vasodilator activity of ANF and sodium nitroprusside suggest a common mechanism of action.