The effects of d- and l-tranylcypromine on the disposition and metabolism of intracisternally administered l-norepinephrine-H3 were studied in rat brain. Both isomers inhibited the deamination of norepinephrine-H3. However, d-tranylcypromine was considerably more potent than the l-isomer in this respect. In addition, the l-isomer of tranylcypromine was found to enhance the disappearance of endogenous and tritiated norepinephrine from brain. Although this action appeared to result from an increase in catecholamine release, the possibility of uptake inhibition could not be eliminated. The l-isomer of tranylcypromine enhanced the disappearance of norepinephrine-H3 from brain when administered both 20 and 90 min following intracisternal injection of the label. Comparable doses of d-tranylcypromine did not exhibit this effect. Larger increases in brain levels of normetanephrine-H3 were produced by d,l-tranylcypromine than by either the d- or l-isomer alone, indicating that the racemic mixture may produce the greatest increase in the interaction of norepinephrine with its postsynaptic receptors.