Butane is the simplest alkane fuel for which more than a single structural isomer is possible. In the present study, n-butane and isobutane are used in a test engine to examine the importance of molecular structure in determining knock tendency, and the experimental results are interpreted using a detailed chemical kinetic model. A sampling valve was used to extract reacting gases from the combustion chamber of the engine. Samples were withdrawn at different times during the engine cycle, providing concentration histories of a wide variety of reactant, olefin, carbonyl, and other intermediate and product species. The chemical kinetic model predicted the formation of all the intermediate species measured in the experiments. The agreement between the measured and predicted values is mixed and is discussed.Calculations show that RO2 isomerization reactions are more important contributors to chain branching in the oxidation of n-butane than in isobutane. Chain branching in isobutane oxidation is dependent on H-atom abstraction reactions involving HO2 and CH3O2 radicals that occur at higher temperatures than RO2 isomerization reactions. Therefore, an isobutane mixture must be raised to a higher temperature than a n-butane mixture to achieve the same overall rate of reaction.