The enantioselectivity of the lipase-catalyzed esterification of 2-(4-substituted phenoxy)propanoic acids was found to be dramatically enhanced by addition of aqueous sodium dodecyl sulfate (SDS) as a new type of additive to the reaction medium, isopropyl ether. The origin of the enhanced enantiomeric differentiation may be attributed to the increased conformational flexibility of lipase triggered by the SDS action, the flexibility of which can be estimated from the changes in the ESR spectra observed for the mobility of a spin label bound to its active-site.