The synthesis of a series of 1-(aminomethyl)phthalans 1b is reported. The radioligand binding to alpha 1- and alpha 2-receptors and the in vitro pharmacology in alpha 1 (rabbit aorta) and alpha 2 (phenoxybenzamine-pretreated dog saphenous vein) tissues were determined and were compared to the activity of the corresponding 1-(aminomethyl)indans. The activity of this series of phthalans was found to be consistent with the electrostatic repulsion hypothesis that was used to design the parent indan (ERBCOP) compounds. The effect of the phthalan ring oxygenation was to somewhat improve alpha 1-receptor potency relative to the 6-ERBCOP indans without having a general effect on the alpha 2-receptor potency. We conclude from the overall pattern of activity that while the norepinephrine type beta-hydroxyl group may be beneficial for binding to the alpha 1-adrenoceptor, it is not required for strong binding to or full stimulation of the alpha 2-adrenergic receptor, provided that the conformational mobility associated with the phenylethylamine is restricted and maintained in a favorable conformation for receptor interaction.