Fundamental reaction pathways for the alkaline hydrolysis of carboxylic acid esters, RCOOR', were examined through a series of first-principle calculations. The reactions of six representative esters with hydroxide ion were studied in the gas phase. A total of three competing reaction pathways were found and theoretically confirmed for each of the esters examined: bimolecular base-catalyzed acyl-oxygen cleavage (B(AC)2), bimolecular base-catalyzed alkyl-oxygen cleavage (B(AL)2), and carbonyl oxygen exchange with hydroxide. For the two-step B(AC)2 process, this is the first theoretical study to consider the individual sub-steps of the reaction process and to consider substituent effects. For the carbonyl oxygen exchange with hydroxide and for the one-step BAL2 process, we report here the first quantitative theoretical results for the reaction pathways and for the energy barriers. The energy barrier calculated for the second step of the B(AC)2 process, that is, the decomposition of the tetrahedral intermediate, is larger in the gas phase than that of the first step, that is, the formation of the tetrahedral intermediate, for all but one of the esters examined. The exception, CH3COOC(CH3)(3), does not have an alpha hydrogen in the leaving group. The highest energy barrier calculated for the B(AC)2 process is always lower than the barriers for the oxygen exchange and for the B(AL)2 process. The difference between the barrier for the B(AL)2 process and the highest barrier for the B(AC)2 process is only similar to 1-3 kcal/mol for the methyl esters, but becomes much larger for the others. Substitution of an alpha hydrogen in R' with a methyl group considerably increases the energy barrier for the B(AL)2 process, and significantly decreases the energy barrier for the second step of the B(AC)2 process. The calculated substituent shifts of the energy barrier for the first step of the B(AC)2 process in gas phase are in good agreement with the observed substituent shifts for the base-catalyzed hydrolysis of alkyl acetates in aqueous solution. All of the calculated results are consistent with the available experimental results and lead to a deeper understanding of previously reported gas-phase experimental observations.