1. Intrathecal injection of ondansetron has the potential to reduce opioid-related side-effects. The aim of the present study was to determine whether this route of administration produces neuraxial injury. 2. Adult, non-pregnant female New Zealand white rabbits received a single bolus injection of a low (40 microg) or high (4.0 mg) dose of ondansetron into the intrathecal space between the 4th and 5th lumbar vertebrae. In some cases, ondansetron was coadministered with morphine (5 microg/kg). Control animals received a bolus injection of normal saline. Behavioural assessments were conducted at 1 and 24 h to determine overt changes in arousal and mobility, followed by histological evaluation of the excised spinal cord. 3. Of 45 animals investigated, 10 rabbits exhibited modest behavioural evidence of spinal injury, the incidence of which was equally distributed between the treatment groups. Haematoxylin and eosin, along with HAM56, staining of cross-sections of the cervical, thoracic and upper and lower lumbar areas revealed mild signs of inflammation. This, too, was equally distributed between the treatment groups, suggesting that any observed neuraxial injury was the result of needle trauma and not ondansetron neurotoxicity. 4. Collectively, these negative findings support conducting further experiments to fully assess the clinical usefulness of intrathecal ondansetron administration.