N-Acyloxyalkylation using 5-phenyltetrazole as a model compound was investigated as a general means of prodrug modification of the tetrazole ring with a view to change the physicochemical properties for improving biomembrane transport. Pivaloxymethylation gave a mixture of 1- and 2- [(pivaloxy)methyl] -5-phenyltetrazole isomers in 1:4 ratio. The structures of the compounds were established by NMR spectroscopy using nuclear Overhauser effect (NOE) difference and heteronuclear multiple bond correlation (HMBC) techniques. The second-order rate constants for hydroxide ion catalyzed hydrolysis of the ester functions of both the isomers were nearly the same, though the two isomers differ in the degree of conjugation between the tetrazole and the aromatic rings as a result of the differences in the extent to which the two rings can assume coplanarity. The values of the second-order rate constants were comparable to those reported for other N-[(pivaloxy)methyl]-substituted compounds, such as derivatives of 5-fluorouracil, indicating that the unique electronic properties of the tetrazole ring do not have a significant effect on the rate of base-catalyzed hydrolytic regeneration of 5-phenyltetrazole, or the potential stability of such prodrugs. However, the hydrolysis of the more sterically hindered 1-[(pivaloxy)methyl] ester in rat plasma was slower than that of the 2-substituted isomer.