A detailed chemical kinetic mechanism has been developed for the oxidation of primary reference fuel (PRF, mixture of n-heptane and iso-octane) in the presence of ethyl tert-butyl ether (ETBE) or ethanol. The mechanism was validated by comparison with the existing experimental data from shock tubes, a jet-stirred reactor, and a flow reactor. ETBE and ethanol are known as octane number improvers. Enhancement of research octane number (RON) by the addition of ETBE and ethanol to PRF has been measured using a cooperative fuel research (CFR) engine. Increase in RON was simulated with the present detailed kinetic mechanism by estimating the critical compression ratio (CCR) for autoignition in a motored engine. The correlation curve between CCR and RON was derived by calculating the CCR for PRF whose composition defines the RON. The kinetic model reproduces observed variations in RON by the addition of ETBE and ethanol to PRF. Those additives showed a very similar effect on RON.