A liquid-solid chromatography radioimmunoassay (LSC-RIA) method for the quantitation of morphine in plasma is described. The detection limit is 1 ng/ml of morphine per milliliter of plasma. Morphine is initially isolated from its inactive hydrosoluble metabolites by LSC, and is then quantified by RIA. Recovery and reproducibilities inter- and intraassay are satisfactory. The procedure uses commercially available granular matrix (Extrelut) and a RIA 125I morphine kit (Abuscreen) and does not require sophisticated analytical techniques. It can be carried out in any pharmacological laboratory. The procedure has been successfully applied to the investigation of morphine kinetics in nine treated patients, via three different administration routes.