Surface perikaryal labeling on immunohistochemical assay for synaptophysin (SYN)--a glycoprotein component of synaptic vesicle membranes--has been posited to distinguish the neoplastic neuronal elements of gangliogliomas from native central nervous system neurons overrun by gliomas invasive of gray matter. To assess the validity of this criterion in the evaluation of intramedullary neoplasms, we screened formalin-fixed, paraffin-embedded sections from 35 histologically unremarkable spinal cords (removed at autopsy) using commercially available monoclonal antibodies to SYN. All specimens exhibited anti-SYN reactivity, which was confined to gray matter, and all evidenced the concentrated deposition of reaction product along the perikarya of large neurons in the anterior horns, Clarke's columns, and intermediolateral cell columns. A majority (23 specimens) contained neurons completely outlined by reaction product rings comparable to those depicted as being pathognomonic of neuronal neoplasia. This phenomenon presumably reflects the rich complement of axosomatic synapses documented in fine structural studies of the normal spinal cord. Surface perikaryal labeling for SYN is not restricted to the neoplastic neurons of ganglion cell tumors and should be cautiously interpreted, particularly when neurosurgical material derives from the spinal cord.