The degradation of methylprednisolone 21-succinate in aqueous solution was examined as a function of pH at 25 degrees by monitoring the initial rates of product formation. In addition to hydrolysis, acyl migration fro the 21-hydroxyl group was found to be an important reaction. The 17-succinate was isolated, and its decomposition to the 21-succinate was followed by the initial rate method. Direct hydrolysis of the 17-ester was much slower than the 17 leads to 21 acyl migration under alkaline conditions. From the rate constants for the forward and reverse acyl migration, it may be concluded that the 21-ester is thermodynamically more stable, even though its alkaline hydrolysis is faster. The hydrolysis of the 21-ester and the reversible rearrangement are subject to intramolecular catalysis by the terminal carboxyl group, for which a kinetic pKa value of 4.5-4.6 was estimated.