A semipermeable surface (SPS) silica column was applied for the simultaneous determination of carbamazepine (CBZ) and its active 10,11-epoxide metabolite (EPO) in plasma following direct injection in LC. The SPS packing material consists of an ODS ligand as the hydrophobic inner phase and a polyoxyethylene network as the hydrophilic outer phase. When a 5-microliters portion of intact plasma was injected onto the column using a mobile phase of phosphate buffer (pH 7.1, ionic strength 0.1)-acetonitrile (4:1, v/v), the plasma proteins were size-excluded, whereas the drug and its metabolite were retained and separated both from each other and from other commonly co-administered drugs such as phenobarbital (PB) and phenytoin (DPH). The calibration graphs (peak area vs concentration) of CBZ, EPO and PB were linear over the therapeutic range of plasma concentration (r greater than 0.998) with good relative standard deviations (RSD less than 3.98%, n = 5). The recoveries from plasma were almost complete (greater than 96.6%). The analysis time was 17 min. The method as developed was applied in studies on the time course of plasma concentrations of unchanged CBZ and EPO after i.v. administration of CBZ to the rat.