Modification of neuromodulator activity by tricyclic antidepressants was evaluated on the basis of changes in transmission in the cat superior cervical ganglion. Intra-arterial doses of 30 μg of desipramine, 90 μg of protriptyline and 120 μg of nortriptyline were equipotent in facilitating the ganglionic depressive action of epinephrine. At these doses, the ganglionic inhibitory effect of norepinephrine was potentiated to a greater extent by protriptyline than by desipramine and nortriptyline; depression of postganglionic potentials by 5-hydroxytryptamine was augmented by desipramine and protriptyline, whereas dopamine was potentiated only by protriptyline. Propranolol, 200 μg, intra-arterially, enhanced the ganglionic suppressive effect of epinephrine but not norepinephrine. Simultaneous administration of propranolol, 200 μg, and desipramine, 30 μg, potentiated the action of epinephrine to a greater extent than either agent alone. © 1972.