Studies of catecholamine concentrations in defined nuclei from the anterior hypothalamic-preoptic regions and the medulla oblongata, known to contribute to cardiovascular control, were measured following acute or chronic methyldopa administration. These studies indicated that methyldopa was enzymatically converted to methyldopamine and methylnorepinephrine, and in some areas to methylepinephrine which replaced endogenous epinephrine. The predominant metabolite was methylnorepinephrine, which accumulated in concentrations higher than endogenous norepinephrine levels. (-)Methylnorepinephrine was found to be 6 times more potent and 75 times more selective for alpha 2-adrenergic receptors than (-) norepinephrine, and it is suggested that this alpha 2-adrenergic receptor action, particularly in the nucleus tractus solitarius, contributes to a major part of the antihypertensive effect of methyldopa.