BACKGROUND AND OBJECTIVES Neurotoxicity of intrathecally administered local anesthetics is generating increased interest. This study was designed to examine the histopathologic effects of intrathecally administered tetracaine. METHODS Sixty Wistar rats randomly received either 20%, 10%, 5%, 3%, 1%, 0.5%, or 0% tetracaine dissolved in 10% glucose solution or no solution via a chronically implanted intrathecal catheter. The spinal cord at L1, posterior and anterior roots and cauda equina were excised 5 days later, sectioned, processed, and prepared for light and electron microscopic examinations. RESULTS Rats treated with tetracaine at 10% or 20% developed lesions in the posterior white matter and posterior roots. Rats injected with 3% or 5% tetracaine developed lesions, which began in the posterior roots close to the spinal cord and extended to the posterior white matter. The lesions were characterized by axonal degeneration. Injections of < or =1% of tetracaine did not cause any pathological changes. CONCLUSIONS Our results suggest that the initial target of intrathecal tetracaine neurotoxicity may be the posterior roots at their entry into the spinal cord, where the axons are devoid of myelin sheath and thus representing a sensitive area for neurotoxic change.