The alpha-adrenoceptor activity of fenoldopam was evaluated in three different in vitro tissue preparations. In rabbit isolated aortic rings fenoldopam displayed weak alpha 1-adrenoceptor antagonist activity (-log KB = 5.41) and displayed no alpha 1-adrenoceptor agonist activity. In contrast, fenoldopam demonstrated moderately potent antagonist properties at the alpha 2-adrenoceptor in two other tissue preparations. In in vitro model systems used for the characterization of alpha 2-adrenoceptors, fenoldopam competitively antagonized the effects of the alpha 2-adrenoceptor agonist B-HT 920. In the dog isolated saphenous vein and in the isolated field-stimulated guinea-pig ileum, fenoldopam antagonized the effects of B-HT 920 with -log KB values of 7.78 and 7.60, respectively. These data indicate that in addition to being an agonist at DA1 receptors, fenoldopam is also a relatively selective antagonist at alpha 2-adrenoceptors.