The opiate etorphine depresses monosynaptic excitatory postsynaptic potentials (EPSP's) elicited in spinal cord cells by activation of dorsal root ganglion cells in murine neuronal cell culture. The depression is reversed by naloxone. Statistical analysis of the synaptic responses reveals that the opiate reduces EPSP quantal content at this synapse without altering quantal size. Therefore, the opiate action is presynaptic and affects transmitter release rather than postsynaptic responsiveness.