A study using an ovine model of transdermal intrathecal catheterization was planned to investigate the neurotoxicity of magnesium sulfate. Nonpregnant Merino cross ewes (n = 8; age, 5 y; weight, 55.0 ± 6.5 kg) were anesthetized for placement of a lumbar intrathecal catheter. The study protocol defined a 5-d recovery period after introduction of the catheter before the administration of test substances (2 mL of 0.9% saline or 50 or 150 mg MgSO4) followed by euthanasia 1 wk later. Although 3 sheep successfully completed the study as planned, one of the remaining 5 sheep was withdrawn when the catheter was accidentally dislodged 2 d after anesthesia; another was withdrawn because of persistent neurologic deficits of the left hindlimb and intense pruritus during the first 24 h after placement of the catheter; and the remaining 3 animals experienced unacceptable complications within the first 4 h of administration of the test substance. These complications included hindlimb weakness, intense irritation or pruritus of the hindlimbs, recumbency, inability to stand, spasm of the hindlimb, and arching of the back. Postmortem examination of 4 sheep with clinical signs revealed similar gross findings: acute, segmental myelomalacia and hemorrhage within the spinal cord parenchyma in the region of the catheter. Histologic changes included segmental areas of acute myelomalacia, consistent with the intraparenchymal placement of the catheter. Postmortem CT imaging of 3 sheep confirmed the location of the catheter within the spinal cord. Procedural refinement for the placement of intrathecal catheters in sheep by avoiding an invasive surgical procedure was unsuccessful. We therefore recommend a complete or partial surgical approach for the insertion of an intrathecal catheter in sheep or fluoroscopy or ultrasonography intraoperatively to confirm correct placement of the catheter.