Highly selective separations are achieved by changing the basis, or mode, of the separation during the separation process. In particular, mode control and mode sequencing Involve serial changes In the composition of the carrier and/or the stationary phase. To achieve this, simple valving circuits can be used with conventional LC apparatus. A review of Initial progress In this area shows that spectacular Improvements In LC performance are coming within reach experimentally.Modern liquid chromatography (LC) becomes more interesting and more powerful as one increases the number of columns. Usually an LC system contains a simple flowthrough sequence of one or perhaps a few columns. If this sequence is branched and switching devices are used, it then becomes possible to exert far more powerful control on the quality of and the basis for the separation. This leads to the idea of column switching, which is our present interest. The principle can be used in any multidimensional separation scheme, but LC offers an especially convenient area for the advantages to be realized.To illustrate, trace organic separations are often made exceedingly difficult by the large number of substances that tend to be present in the extracted sample, by the similarities among the given analytes (sought-for constituents), and by the need to remove major components that may be present in the extract. Sequential separation techniques are well suited to such problems. To see this, consider that practically unlimited separation capability is possible if the selectivity is systematically changed during the separation process (1). This involves variable combinations of column, carrier, and detector which cooperatively contribute to the overall system selectivity. The advantages of boosting the detector selectivity modes (hyphenated systems) was reviewed by Hirshfeld (2). Here I will review the advantages of a modern approach to sequential separation systems, also known as column switching, multidimensional chromatography, stationary-phase programming, mode switching, selectivity switching, and coupled columns, among other terms.The concept of mode, as a chromatographic property, might appear to be ambiguous, since it usually refers to the separation mechanism which the chromatographic system is intended to provide. It should be understood that the mode and the type of stationary phase are not necessarily the same. The mode, or separation mechanism, depends on the overall interactive relationship between the analyte, the carrier, and the substrate. Usually, the chromatographic mode is considered to be based on the nature of the column stationary phase. Thus, adsorption requires an adsorbent, ion exchange on ion exchanger, and so on. However, these modes are not realized unless specific conditions are met. Under certain