Nonselective beta-adrenergic blockers have been reported to affect endothelium-dependent responses in isolated blood vessels in the following ways: (a) cause endothelium-augmented direct relaxations; (b) facilitate the endothelium-dependent relaxations evoked by alpha 2-adrenergic activation, or by acetylcholine; (c) augment the intraluminal release of vasodilator prostanoids, and (d) inhibit endothelium-dependent contractions to anoxia. Important species differences exist in terms of the endothelium-dependent effects of the compounds. If they were to occur in the intact organism, the endothelium-dependent effects of the beta-adrenergic blockers could help to explain their vasodilator properties.