A selective and sensitive reversed-phase HPLC method was developed for the determination of the antidepressant paroxetine in plasma. The method is based on the purple chromogen formed by a displacement reaction of paroxetine with 7,7,8,8-tetracyanoquinodimethane (TCNQ) in acetonitrile at 80 degrees C for 20 minutes. For the assay, the drug was extracted from 1 mL of plasma with chloroform and, after sample alkalinization, derivatized with TCNQ; then the reaction mixture was directly injected into a C18 column. Desipramine was used as internal standard. The mobile phase was acetonitrile-water (70:30) at a flow-rate of 1.0 mL/min, and the derivatives were eluted at 13.1 and 15.5 minutes for paroxetine and desipramine, respectively, and detected at 567 nm. Calibration curve was found linear over the range of 20-400 ng/mL, and the detection limit was 2 ng/mL at a signal-to-noise ratio of 3/1. Recoveries determined for 3 concentrations range between 81.3% and 88.1%. Intraday and interday relative standard deviation values were found to be within 3.8%-13.5% and 8.2%-14.6%, respectively. With this developed method, a pharmacokinetic study was performed for paroxetine.