The central focus of the Singleton research group is the study of organic, organometallic, and bioorganic reaction mechanisms, and the key tool that we use in these studies is the determination o kinetic isotope effects (KIEs). In the mid-1990's, we developed a method for the high precision combinatorial determination of small KIEs at natural abundance by NMR. Its direct applicability to complex unlabeled reactants makes this methodology 1-2 orders of magnitude faster than studies requiring labeling. At the same time, it is much more versatile - our technique can look at a great number of reactions that would have been impractical or impossible to study by labeling or mass spectral methods, and the choice of reactants can be readily changed in response to each new experimental result. The simultaneous determination of a complete set of 13C, 2H, and 17O isotope effects possible with our methodology provides a much greater level of information than available from conventional methods. In addition, substantial evidence has accumulated supporting the reliable accuracy of our results.