A highly sensitive gas-liquid chromatographic method with electron capture detection of clonidine in plasma is described. The alkaline samples (100-200mul) are extracted into cyclohexane-butanol (9:1), re-extracted into 0.1 N sulphuric acid, made alkaline and back-extracted into cyclohexane-butanol. The pentafluorobenzyl derivatives of clonidine and the internal standard 2,-(2,4-dichlorophenylamino)-2-imidazoline are then formed, and excess of reagent is removed by solvent extractions. The minimum detectable quantity (MDQ) of clonidine and the internal standard are 2.5.10(-16) mol/sec. (3.3 picogram) and 2.8.10(-16) mol/sec (5.9 picogram), respectively. The smallest amount of clonidine which can be determined in plasma samples with a precision of less than 20 per cent S.D. is 200 picogram. The time course of clonidine in plasma after intravenous administration of 500 mug/kg to rats revealed that the data best fit a three-compartment open model.