An animal model which allowed repetitive sampling of CSF is described. It had a wide potential application and was used to study the passage of clonazepam into the central nervous system. A highly sensitive clonazepam assay is described which allow measurement of CSF and free serum concentrations as low as 0.5 ng/ml. Clonazepam passed rapidly into the central nervous system and its CSF concentration closely approximated to the concentration of unbound clonazepam in serum. Protein binding of clonzaepam in the sheep was 90-95%.