A combined thin-layer and gas-liquid chromatographic (TLC-GLC) procedure for determination of tricyclic antidepressant drugs in urine is described. GLC on 1.5% OV-17 was utilized to analyzed basic urine extracts directly for the tricyclics and to confirm the identity of spots extracted from thin-layer chromatograms, and TLC was used to confirm the results of these GLC screens. Lower limits of sensitivity for the thin-layer spot extraction procedure were found to range from 2 mug/ml for amitriptyline and imipramine to 10 mug/ml for desipramine and nortriptyline. Turn-around-times for the GLC tricyclic screens were usually less than 1 h. The finding that nortriptyline and desipramine were chemically altered under various extraction conditions was used as a means of confirming the identity of these drugs, and the identity of these chemically altered derivatives was discussed with reference to their low resolution mass spectra.