a-Methyldopa acts through a metabolite in the central nervous system. Of the three metabolites most prominently considered as potential mediators of a-methyldopa hypotension -amethyldopamine, a-methylnorepinephrine (MNE), and a-methylepinephrine (ME) -ME is the most potent depressor agent following intravenous infusion into rats, following injection into the lateral ventricle, and following injection into the solitary tract nucleus (NTS). The depressor effect of ME in the NTS is attenuated as effectively by timolol as by yohimbine, while the combination of both timolol and yohimbine completely abolishes the pharmacological activity of ME in the NTS. ME is approximately eightfold more potent than MNE in the NTS and also has a greater susceptibility to timolol attenuation. (Hypertension 6 (Suppl II): II-45-II-50, 1984) KEY WORDS • methyldopa • methylepinephrine • methylnorepinephrine methyldopamine • CNS • blood pressure From the Division of Clinical Pharmacology, Vanderbilt University, Nashville, Tennessee 37232.