A new concept for cleanup, based on volume overloading of the cleanup column, has been developed for on-line coupling of gel permeation chromatography (GPC), solid-phase extraction (SPE), or both, to gas chromatography (GC). The principle is outlined and the applicability demonstrated by the determination of pesticide residues in food matrixes using integrated and automated cleanup-GC-MS. Compared to conventional approaches for on-line cleanup-GC, the new technique involves introduction of much smaller volumes (e.g., 2-20 microL) into the GC without sacrificing method LODs. The much smaller injection volumes involved greatly simplify on-line coupling, improve robustness, and increase attractiveness for implementation in routine laboratories.