The effects of Niamid (nialamide) were studied on the continuity of sympathetic transmission and on cardiovascular response to vasoactive drugs in conscious hypertensive dogs and anesthetized cats. Niamid did not produce any change in either the systolic pressure or in the pressor effects of DMPP and norepinephrine unless toxic symptoms were present in conscious hypertensive dogs. Close intra-arterial injections of large doses of Niamid and Marsilid (iproniazid) for periods of up to 4 hours were without effect on evoked ganglionic action potentials in the superior cervical sympathetic ganglion of the cat. Depression of the carotid occlusion reflex was seen after administration of Niamid and could represent an inhibition of vasomotor center activity since it occurred when the peripheral responses to vasoconstrictor substances were not reduced. However, the spontaneous action potentials recorded from single preganglionic fibres of the cervical sympathetic nerves of the cat were increased by Niamid during the early stages of hypotension which suggests an exclusively peripheral mechanism during early stages of hypotension. Niamid increased the pressor effects of vasopressin, tyramine, epinephrine and norepinephrine and the depressor effects of iso-prenaline, histamine and acetylcholine. Evidence was obtained which suggested that a circulating isoprenaline-like substance formed by monoamine oxidase (MAO) inhibitors might be responsible for the depression of the carotid occlusion reflex produced by Niamid. Niamid and Marsilid prevented the restorative effect of norepinephrine on the pressor response of tyramine in the reserpine pre-treated spinalized cat. However, the effects of tyramine in the normal cat were potentiated. This would indicate that Niamid and Marsilid only interfere with the tissue binding of catecholamines and not their release. These experiments show that neither an adrenolytic nor a ganglionic blocking action are responsible for the hypotension seen during the administration of these compounds. It is suggested that hypotension associated with MAO inhibition may be due either to an inhibitory effect on central vasomotor control, to changes in cell permeability, binding and release of catecholamines unrelated to MAO inhibition or to the formation of isoprenaline-like compounds as a consequence of MAO inhibition.