Isoprenaline produced concentration-dependent contractions of the in vitro canine saphenous vein which were attenuated by phentolamine (10(-6) M) and pacing-induced heart failure. Both at control and peak heart failure, a biphasic response was seen in the dorsal pedal artery, consisting of an initial relaxation followed by a contraction; phentolamine and heart failure enhanced the relaxation component. In the presence of propranolol, the isoprenaline-induced contraction was sensitive to yohimbine, but resistant to prazosin. Therefore it is concluded that isoprenaline interacts not only with vascular beta-adrenoceptors, but also with alpha 2-adrenoceptors. Endothelial denudation resulted in a diminished response to isoprenaline in control saphenous vein and dorsal pedal artery but not in vessels from dogs with heart failure. The observation that the contractile response to isoprenaline diminishes in heart failure implies a specific down-regulation of peripheral vascular alpha 2-adrenoceptors.