Epidural clonidine is an alternate way to treat severe pain in man. The cerebrospinal fluid (CSF) and plasma concentrations resulting after epidural, intravenous (i.v.) or intramuscular (i.m.) clonidine, 3 ug/kg b.w. have been determined by a sensitive gas chromatographic method. A porcine model was used, where the epidural and intrathecal spaces were cannulated via the atlanto-occipital membrane. After epidural administration of clonidine the CSF concentrations were maximal 20 minutes after the injection, 129 +/- 24 ng/ml (mean +/- S.D.). Clonidine was eliminated from CSF with an apparent half-life of 26 +/- 8.2 minutes (mean +/- S.D.). The plasma concentrations stayed below 1 ng/ml. Low plasma and undetectable CSF concentrations resulted after i.v. clonidine. Thus, epidural clonidine readily penetrates the dura mater into the CSF, and there is a marked gradient between CSF and plasma.