Tritiated-α-methylprednisolone-21-acetate was prepared in a dosage form comparable to commercial Depo-Medrol and administered to adult cats either intracisternally or intraperitoneally. Therapeutic amounts of tritiated methylprednisolone acetate were taken up rapidly from the subarachnoid space of cats into the central nervous system to reach levels five to ten times higher than could be attained by systemic injection. Plasma steroid levels were similar whether the drug was placed in the peritoneal or cisternal space. Although the steroid concentration in brain declined rapidly during the first 24 hours after intrathecal injection, steroid was still detectable seven days later. White matter regions tended to attain and retain larger amounts of steroid than gray. Brain steroid levels after intrathecal administration, probably represent a steady state between the rate of diffusion of steroid into the brain from the cerebrospinal fluid (CSF) and its rate of removal by the circulation. Provided that high CSF steroid levels are attained, higher and more prolonged therapeutic brain levels will result after intrathecal administration than by other routes.