Abstract: Langendorff's hearts of 59 guinea pigs and 16 cats were used to study the actions of phenelzine sulphate (Nardil) on coronary flow, heart rate, and contractile force, together with its mechanism in relation to catecholamines and 5-HT. 1. For guinea pigs, phenelzine in concentration of 10^-6M exerted a significant inhibition on beating hearts with a concomitant increase of coronary flow (+36%), which was remarkably more than that on fibrillating hearts (+8%). It was thus demonstrated that about 3/4 of the augmentation of coronary flow on beating hearts were attributed to a diminution of the extra-coronary resistance from a reduction of the contractile force, whilst the rest (1/4) was due to a direct coronary dilatation. For cats, phenelzine (10^-6M) caused no significant alterations in heart rate and contractile force, and, consequently, the increments of coronary flow in beating and fibrillating hearts (+8% and +9% respectively) approximated to each other. 2. The decrease of coronary flow (-23%) induced by pituitrin (0.5 unit/1) on beating hearts of guinea pigs was converted to an increase (+18%) by perfusion of phenelzine (10^-6M). If the guinea pigs were pretreated with phenelzine 15mg/kg/day for 6 days, the pituitrin became practically ineffective. 3. The lack of significant difference between normal hearts and reserpinized hearts in response to phenelzine, as well as the absence of sympathomimetic action of phenelzine on the hearts, indicated that the cardiac effects of phenelzine in guinea pigs could hardly be ascribed to the release of catecholamines. 4. The hearts of reserpinized guinea pigs were more sensitive to 5-HT than those of normal ones. The hearts after perfusion of phenelzine or the hearts of phenelzinized guinea pigs, however, showed no marked augmentation in reactivity toward 5-HT. These results suggested that cardiovascular effects of phenelzine are probably not mediated by accumulation of 5-HT.