The early hypotensive action of intravenous guanethidine in rabbits, rats and cats anaesthetized with urethane is reversed after pretreatment with iproniazid. The fall in blood pressure following injection of guanethidine in rabbits is reduced after previous administration of reserpine. Reserpine, like adrenalectomy and splenectomy, suppresses the early pressor effect of guanethidine in cats anaesthetized with chloralose. Guanethidine inhibits the action of tyramine and nicotine, but potentiates the effect of noradrenaline on isolated rabbit atria. Guanethidine is also a weak inhibitor of monoamine oxidase activity. The results are discussed and compared with those shown by reserpine. It is concluded that the early effects of guanethidine are mainly due to the release of endogenous catechol amines.