A fatal case of inadvertent intrathecal entry of an ionic contrast medium during a nephrogram is reported. The patient developed seizures and failed to regain consciousness following the event. Computerized tomography revealed extensive intraventricular and subarachnoid hyperdensity and cerebrospinal fluid analysis revealed markedly elevated protein content. At autopsy a traumatic communication between the kidney and thecal sac was identified. Histopathological examination revealed cytoplasmic shrinkage and eosinophilia, nuclear pyknosis and karyorrhexis in neocortical neurons. Central chromatolysis was seen in brain stem motor nuclei and anterior horn cell neurons. The neuropathological findings appear to be on the basis of direct neurotoxicity from the contrast medium and excitotoxic injury secondary to seizure activity. Inadvertent intrathecal administration of ionic contrast media is a rare occurrence with often fatal consequences despite aggressive medical management.