Background: Intravascular injection of particulate steroids during cervical nerve root blocks has been postulated to be a source of catastrophic neurologic complications that might be avoided with the use of non-particulate steroids. The objective of this study was to compare the effects of direct intravascular injection of particulate and non-particulate steroids on the spinal cord and central nervous system. Methods: Eleven adult pigs underwent direct injection, under fluoroscopic guidance, into the vertebral artery while under general anesthesia. A particulate steroid (methylprednisolone) was injected into four animals (Group 1), whereas seven animals received a non-particulate steroid (dexamethasone in four animals [Group 2] and prednisolone in three [Group 3]). Following injection, the animals were assessed by direct observation of physical activity and with magnetic resonance imaging. After the animals were killed, brain and spinal cord material was retrieved, fixed in paraformaldehyde for one week, and then subjected to histopathologic analysis. Results: All four animals in Group 1 failed to regain consciousness after the injection and required ventilatory support. The animals in Groups 2 and 3 recovered fully and demonstrated no evidence of neurologic injury. Magnetic resonance imaging revealed upper cervical cord and brain stem edema in Group 1, but not in Groups 2 and 3. Histologic analysis showed early evidence of hypoxic and ischemic damage - specifically, early eosinophilic neuronal necrosis, nuclear condensation, white-matter pallor, and extracellular edema - in Group 1 but not in Groups 2 and 3. Conclusions: These data suggest that one etiology of neurologic complications following cervical nerve blocks may be inadvertent intravascular injection of particulate steroids, as all animals injected with methylprednisolone had neurologic deficits while none of the controls injected with non-particulate steroids were affected. To our knowledge, this study is the first to demonstrate that particulate steroids cause neurologic deficits and to suggest that use of non-particulate steroids might prevent such complications.