The influence of removing the endothelial cells on the alpha-receptor-mediated contractile response in segments of rat aorta was investigated using agonists with a range of affinity for alpha 1- and alpha 2-receptors. The preferential alpha 1-agonists were methoxamine, cirazoline, ST 587, and Sgd 101/75 and the preferential alpha 2-agonists were B-HT 920, clonidine, and guanfacine. When the endothelium was intact, the intrinsic activity (compared to noradrenaline) varied widely (0.0-0.7) for both groups of agonists. After removal of the endothelium the intrinsic activity was increased in each case to that of noradrenaline, or close to it. Furthermore, an increase in potency was obtained for each agonist, although to different degrees. No correlation, however, was found between the selectivity of the agonists and the degree of enhancement caused by the removal of the endothelium, in terms of either the intrinsic activity or the potency. Moreover, the use of the selective alpha 2-receptor antagonist rauwolscine on intact tissues did not mimic the effect of removing the endothelium. Therefore, the alpha-receptors of the endothelium could not be classified as either of the alpha 1- or alpha 2-subtype.