Pretreatment of strips of rabbit aorta with 10(-3) M sodium cyanide reduced contractions to 10(-8) through 10(-4) M norepinephrine (NE) added cumulatively. This antagonism by cyanide was not altered by 4 X 10(-6) M ouabain or verapamil, suggesting a lack of involvement of Na+, K+ ATPase or of calcium influx in the antagonism. Cyanide potentiated contractions caused by 3 X 10(-2) M potassium, but reduced contractions induced by higher potassium concentrations. Because the antagonism of higher concentrations of potassium and NE were similar, it seems that selective actions on different calcium pools are possibly not involved in the antagonism of agonist-induced contractions. 10(-2) M cyanide contracted rabbit aorta with a mean contraction 16% of that induced by 10(-4) M NE. These contractions were potentiated by pretreatment with 4 X 10(-6) M ouabain and 4 X 10(-6) M verapamil but were unaffected by the serotonin antagonist 2-bromo lysergic acid diethylamide, 10(-4) M (2-BrLSD), the alpha adrenergic antagonist phentolamine, 4 X 10(-5) M, the H1 antihistaminic pyrilamine, 10(-5) M, or the antimuscarinic atropine, 10(-6) M. The contractions were reduced by 10(-4) M 4,4'-di-isothiocyano-2,2'-stilbene disulfonic acid (DIDS) or chlorpromazine. The reduction may be due to a blockade of anionic channel mechanisms facilitating entry of cyanide into the vascular smooth muscle cell, as both of these agents can block anionic channels in other tissues.