Box 78, Cardiff CF1 lXL, UK Combined gas chromatography mass spectrometry, because of its ability to provide both high sensitivity and specificity, has become a vital technique for the identification and quantitation of natural and synthetic chemicals in a wide variety of areas. Unfortunately, a very large number of organic compounds are not directly amenable to gas chromatography since they are thermally labile and/or of low volatility. Chemical modification of compounds of interest can assist in some cases, but it is not universally applicable. High performance liquid chromatography has been increasingly utilized for studies of compounds of these types since heat is not usually involved in the analysis. Combined liquid chromatography mass spectrometry would lend a new dimension to these studies, enabling the separating ability of the liquid chromatograph to be combined with the sensitivity and specificity of the mass spectrometer. Approaches to liquid chromatography mass spectrometry are discussed. Using examples from our liquid chromatographic mass spectrometric studies of natural compounds, drugs and pesticides, the current abilities of such systems to identify and quantify natural and synthetic chemicals present in a complex matrix of other chemicals are described.