The palladium(II) aqua complex cis-[Pd(en)(H(2)O)(2)](2+) catalyzes the alcoholysis of urea into alkyl carbamate and ammonia. The observed rate constants for the ester formation fall in the range from 1.8 x 10(-)(5) to 5.9 x 10(-)(1) min(-)(1) at 313 K and pH 3.3, depending on the alcohol. This catalyzed reaction is at least 10(5) times faster than the uncatalyzed alcoholysis of urea under the same conditions. This is the first example of catalytic, nonhydrolytic cleavage of the amide bond in urea. The following steps in the mechanism of the methanolysis reaction are studied quantitatively: binding of urea to the catalyst in the presence of various alcohols or various concentrations of water, direct methanolysis of O-bound and N-bound urea, formation of carbamic acid (NH(2)COOH) coordinated to palladium(II) via the nitrogen atom, methanolysis of this intermediate, and the fast dissociation resulting in free methyl carbamate. Ammonia, a product of alcoholysis, inhibits this reaction by binding to palladium(II). When, however, ammonia is sequestered by the silver(I) cation, alcoholysis becomes relatively fast, and catalytic turnover is achieved. Various alcohols are compared in their reactivity toward urea. The effects of nucleophilicity, steric bulk, size, and additional hydroxyl groups (in diols) are examined. The intramolecular alcoholysis in the 2,6-dithia-1,8-octanediol complex cis-[Pd(C(6)H(14)O(2)S(2))(H(2)O)(2)](2+) results in at least 100-fold rate enhancement relative to the intermolecular alcoholysis by cis-[Pd(en)(H(2)O)(2)](2+). Alkyl carbamates do not hydrolyze further into carbamic acid and alcohol. Aryl carbamates do hydrolyze further, and this reaction requires the palladium(II) aqua complex as a catalyst. Carbamic acid then spontaneously decomposes into carbon dioxide and ammonia. Observed rate constants for the appearance and disappearance of aryl carbamates agree with the relative nucleophilicities of aryl alcohols. This study of the catalysis by a metal complex may contribute to the understanding of the metalloenzyme urease. We propose a new method, alcoholysis, for cleaving amide bonds in peptides and proteins.