The present investigation was designed to elucidate the mechanism of action of metaraminol. The responses of arterial pressure and of myocardial contractile force to graded doses of metaraminol were compared in dogs and in animals which were catecholamine-depleted by the prior administration of reserpine. In the latter animals, these responses were strikingly reduced but not completely abolished. Infusions of norepinephrine to the reserpinized animals restored the responses to mataraminol towards normal. The administration of metaraminol was found to release norepinephrine from the heart into the coronary sinus blood. Two-hour infusions of metaraminol resulted in a reduction of atrial norepinephrine content which averaged 55.5% of the control levels, and markedly reduced the hemodynamic responses to single injections of tyramine and metaraminol. ft is concluded from these studies that the major action of metaraminol results from the release of norepinephrine and that prolonged administration of the drug results in reduction of tissue norepinephrine stores. However, the possibility that metaraminol has a direct effect was not excluded.