Boron-doped diamond (BDD) electrodes have been examined for the electrochemical detection of six tricyclic antidepressant drugs (TCAs): iniipramine, desipramine, clomipramine, amitriptyline, nortriptyline, and doxepin. Cyclic voltammetry, flow injection analysis (FIA) and HPLC with electrochemical detection have been used to study the oxidation reactions and to detect the TCAs. At diamond electrodes, well-defined and highly reproducible voltammograms were obtained for all six drugs with a signal to background (S/B) ratio about 2-4 times greater than those at glassy carbon electrodes. Diamond is the first electrode material to show well-defined voltammograms for nortriptyline due to its wide potential window. In the FIA-mode, at an operation potential of 0.85 V versus Ag \ AgCl, diamond exhibited a background current of 7 nA with rapid stabilization (15 min) conversely to the case of GC, which appeared to stabilize after I h, but again increased thereafter. The analytical peaks of HPLC for the TCAs were well resolved. Linear calibration curves were linear over the ranges from 0.05 to 100 muM. The limits of detection (S/N = 3) were 3 nM for iniipramine and desipramine, 0.5 nM for clomiprarnine, 163 nM amitriptyline, 1080 nM for nortriptyline and 92 nM for doxepin. The electrodes have shown reproducible results over several days of analysis. This method has been applied for the determination of imipramine and desipramme in plasma samples. The BDD surface was reproducible with no adsorption of blood components during plasma analysis. This work shows the promising use of diamond as an amperometric detector in HPLC, especially for TCA analysis.