A high performance liquid chromatographic method with diode-array detection (HPLC/DAD) for simultaneous screening of 25 antidepressants is presented. After single-step liquid-liquid extraction at pH9.5 using chloroform/2-propanol/n-heptane (60/14/26, v/v), the substances are eluted on a Novapak C18 4-microns column (300 x 3.9 mm, id), with methanol/tetrahydrofuran/pH 2.6 phosphate buffer (65/5/30, v/v) as the mobile phase (flow rate 0.8 ml/min). Full UV spectra from 200 to 400 nm are recorded on-line during the entire analysis and may be automatically compared to spectra stored in a library. The analysis is performed in 14 min. The method is simple, rapid, and highly specific.