The electron-transfer-catalyzed Diels-Alder reaction of indole and 1,3-cyclohexadiene was studied by a combination of experimental and theoretical methods. The (13)C kinetic isotope effects were determined at natural abundance by NMR methodology. B3LYP/6-31G* calculations allow for the first time a quantitatively accurate description of the different possible pathways and provide the basis for an analysis of the experimentally observed isotope effects. The computational results, in conjunction with experimental observations, show that the reaction has a stepwise mechanism that is initiated by attack of the diene into the 3-position of the indole. Numerical simulation of the experimentally observed isotope effects shows that the first step is rate-determining and that the electron exchange in the reactant contributes partially to the overall isotope effect. The combination of electronic structure theory, experimental isotope effects, and numerical simulation thus allows a detailed analysis of a complex reaction mechanism.