In this paper we report the first example of peptide hydrolysis catalyzed by a polyoxometalate complex. A series of metal-substituted Wells-Dawson polyoxometalates were synthesized, and their hydrolytic activity toward the peptide bond in glycylglycine (GG) was examined. Among these, the Zr(IV)- and Hf(IV)-substituted ones were the most Wells-Dawson type polyoxometalate K15H[Zr(alpha(2)-P2W17O61)(2)]center dot 25H(2)O reactive. Detailed kinetic studies were performed with the Zr(IV)-substituted which was shown to act as a catalyst for the hydrolysis of the peptide bond in GG. The speciation of K15H[Zr(alpha(2)-P2W17O61)(2)]center dot 25H(2)O which is highly dependent on the pD, concentration, and temperature of the solution, was fully determined with the help of P-31 NMR spectroscopy and its influence on the GG hydrolysis rate was examined. The highest reaction rate (k(obs) = 9.2 (+/- 0.2) x 10(-5) min(-1)) was observed at pD 5.0 and 60 degrees C. A 10-fold excess of GG was hydrolyzed in the presence of K15H[Zr(alpha(2)-P2W17O61)(2)]center dot 25H(2)O proving the principles of catalysis. C-13 NMR data suggested the coordination of GG to the Zr(IV) center in K15H[Zr(alpha(2)-P2W17O61)(2)]center dot 25H(2)O via its N-terminal amine group and amide carbonyl oxygen. These findings were confirmed by the inactivity of K15H[Zr(alpha(2)-P2W17O61)(2)]center dot 25H(2)O toward the N-blocked analogue acetamidoglycylglycinate and the inhibitory effect of oxalic, malic, and citric acid. Triglycine, tetraglycine, and pentaglycine were also fully hydrolyzed in the presence of K15H[Zr(alpha(2)-P2W17O61)(2)]center dot 25H(2)O yielding glycine as the final product of hydrolysis. K15H[Zr(alpha(2)-P2W17O61)(2)]center dot 25H(2)O also exhibited hydrolytic activity toward a series of other dipeptides.