Enthalpy barriers for gas phase asymmetric alkyl cation transfer reactions between neutral and protonated alcohols in mixed alcohol systems have been calculated by B3LYP, MP2, and G3(MP2) computational methods. As expected, on the basis of the proton affinities of the alcohols, the enthalpy barrier for transfer of the larger alkyl cation is calculated to be lower than that for transfer of the smaller alkyl cation. A linear relationship between the difference in gas basicity (GB) between the alcohols and the enthalpy barrier is observed for the less favorable alkyl cation transfer reactions. The slope of the regression line is 0.55, and the intercept (at DeltaGB = 0) is found to be -22.5 kJ mol(-1), which is extremely close to the enthalpy barriers for symmetric alkyl cation transfer. This relationship is discussed in the context of the Hammett relationship. Experiments conducted on the reaction of protonated ethanol with O-18-labeled methanol established that about 7.8% of the protonated ethyl methyl ether formed was via the less favorable methyl cation transfer. This experimental value agrees well with the 8.5% predicted based upon the calculated difference in energy barriers between ethyl and methyl cation transfer (6.1 kJ mol(-1)). This work shows that in the gas phase, the protonated ether products in mixed alcohol systems are formed via two competing S(N)2 reactions and that the efficiency of the less favorable alkyl cation transfer reaction increases as the difference in proton affinity of the two alcohols decreases.