Unexpected spinal anesthesia, occurring after peripheral nerve blocks close to the spine, may be caused by a centripetal spread of the local anesthetic along the injected nerve to the spinal cord. In order to analyze the pathway of such a spread, a radioactive local anesthetic mixed with a fluorescent dye was injected into difrerent compartments of the rabbit sciatic nerve, and the early distribution of these tracers was studied by scintillation counting and fluorescence microscopy. Epineurial (extrafascicular) injections were of low injection pressure (25-60 mmHg) (3.3-7.9 kPa) and limited spread, while endoneurial (intrafascicular) injections reached higher pressures (300-750 mmHg) (39.9-99.7 kPa) and caused a rapid spread over long distances within the fascicle. The sacral plexus seemed difficult to pass. However, 20% of endoneurial injections reached the spinal cord, where the injectate primarily spread in the thin subpial space. Our experimental findings suggest that intraneural injections of local anesthetics are responsible for the reported cases of unexpected spinal anesthesia due to inadvertent intrafascicular spread. Although intrafascicular injections are rarely made, we recommend that intraneural injections of local anesthetics or other solutions close to the spine should be avoided, as they may cause unexpected spinal anesthesia or lesion of the cord.