This case report describes the clinical course of a patient who inadvertently received a massive intrathecal cefazoline overdose through a lumbar drain, which had been placed after trans-sphenoidal surgery for a pituitary adenoma. She received high-dose barbiturate therapy and was monitored with electroencephalography (EEG), somatosensory evoked potentials (SSEP), brainstem auditory evoked potentials (BAEP) and transcranial Doppler ultrasound (TCD). No cerebrospinal fluid (CSF) exchange was performed, but CSF was drained continuously with daily CSF-cefazoline level monitoring. Despite the extremely toxic dose, the patient soon recovered completely.