The effect of solvent anisotropicity on ester hydrolysis was studied in lyotropic liquid crystalline phases. Procaine hydrochloride and two of its quaternary derivatives, procaine methyl chloride and procaine ethyl chloride, were employed as substrates, and an aqueous gel consisting of 55% polyoxyethylene tridecyl ether, identified as a neat smectic system, was chosen as the solvent medium. Pseudo‐first‐order rate constants for the hydrolysis were obtained in the apparent pH range 8.80‐11.40, at a temperature of from 30 to 50°, over a surfactant span of 50‐65% in the mesophase. Rate measurements were also carried out in aqueous media and in mixed aqueous systems containing polyethylene glycol 300 and 400. The esters were located within the aqueous polyoxyethylene layers as indicated by their UV spectral characteristics. The reaction rates were found to be considerably slower (300‐ to 1100‐fold) in the liquid crystalline phases than in aqueous media. The reactions, as they occur within the smectic phase, are characterized by relatively low apparent activation energies and by large negative entropies of activation.