The introduction of hyphenated chromatographic-spectroscopic techniques represented a substantial step-forward for Systematic Toxicological Analysis (STA), increasing the amount and quality of information obtainable from the analysis of a biological sample, and enhancing the possibilities of identifying unknown drugs and poisons. STA methods based either on GC-MS or on HPLC-UV published in the last decade are reviewed in this paper. The different analytical phases, i.e. sample preparation (pretreatment, extraction, derivatisation), chromatographic separation and detection/identification are examined in detail in order to emphasise the complementarity of the two approaches, In addition, the first STA method based on HPLC-MS is illustrated and some applications of TLC-UV to drug screening are also described, Finally, an overview of semi- and fully-automated STA methods is given. (C) 1999 Elsevier Science B.V. All rights reserved.