Dopamine, serotonin and related compounds (referred to collectively as biogenic amines) were found to modify transmission at the presumably cholinergic synapse made by an axon in the right visceropleural connective onto cell R15 of the abdominal ganglion of Aplysia californica. (1) With chronic application, dopamine hyperpolarizes R15, and serotonin depolarizes R15. Both actions upon the membrane potential desensitize in 10 min. All the actions described below were studied with chronic perfusion of the biogenic amines after desensitization of this postsynaptic action. (2) The biogenic amines drastically reduce the size of the EPSP evoked at the synapse under investigation; but they do not alter the ACh potential evoked in the soma of R15. (3) The biogenic amines reduce the amplitude of synaptic depression. The relationship between the effects of the amines on the size of an isolated EPSP and on synaptic depression differed from this relationship as affected by post-tetanic potentiation (PTP) or by changes in the Ca2+-Mg2+ balance. (4) The biogenic amines increase frequency facilitation, when the latter is defined as the ratio of the facilitated to the isolated EPSP. However, the absolute magnitude of the facilitated EPSP is always reduced at long times after introduction of the agent; shortly after introduction of the biogenic amines the absolute magnitude of the facilitated EPSP is unaffected in most preparations.