Determination of oxypertine, (5, 6-dimethoxy-2-methyl-3-[2-(4-phenyl-1-piperazinyl)-ethyl] indole), in the human serum by high performance liquid chromatography (HPLC) was described. The compound in the serum was extracted with ether after the addition of sodium carbonate solution. After evaporation of the solvent, the residue was dissolved in HPLC mobile phase composed of methanol-acetic acid-sodium acetate-water (100 : 0.5 : 0.025 : 0.2). An aliquot of the solution was injected onto a high performance liquid chromatograph equipped with Zorbax SIL stationary phase and ultraviolet (UV) detector at 254 nm. Elution was carried out by the above-mentioned mobile phase, and the peak of oxypertine appeared after all the UV-absorbing components in the serum was eluted. The recovery of oxypertine from the normal pooled-serum by this method was 99.5% (n=5, S.D.=2.95), and the limit of detection was 11 ng per ml of serum.