The stable isotope method has been used successfully in bioavailability studies for highly variable drugs that have extensive first-pass metabolism and exhibit large intra-subject variation in clearance. Recently this technique has been extended to bioequivalence studies where labeled so-Lution is intravenously infused in both occasions while test and reference formulation are admini-stered. This report discusses the advantages ami disadvantages of the stable isotope method and its application in bioavailability and bioequivalence studies of highly variable drugs and drug delivery systems.