In sympathetic neurons, axotomy induces a marked depression in synaptic transmission. We asked whether the decrease in synaptic efficacy observed in a given axotomized cell is more severe if most of the postsynaptic neurons are also injured. Accordingly, we studied if the synaptic depression induced by axotomy in neurons with axons running in a postganglionic nerve is influenced by section of other postganglionic nerves. The excitatory postsynaptic potentials evoked by preganglionic stimulation were recorded intracellularly in an in vitro preparation of the superior cervical ganglion. Eight days after cutting the inferior postganglionic nerve, postsynaptic potentials recorded from neurons projecting through this nerve were smaller (median = 6 mV, n = 62) than the controls (median = 34 mV, n = 89), but were similar to those found after sectioning the inferior nerve plus most postganglionic nerves (median = 5 mV, n = 70). If the inferior nerve was left intact, but most postganglionic branches were cut, the synaptic potentials recorded from inferior nerve neurons were normal (median = 33 mV, n = 77). It is concluded that the synaptic depression induced by axotomy in a sympathetic neuron is not affected by axotomy of nearby ganglion cells, even if they share part of their presynaptic axons. This suggests that the effect of axotomy is restricted to the synaptic terminals on the injured neuron.