The aromatic hydrogen nuclei of tyrosine are photochemically labile and exchange with deuterons in neutral D2O solution. The site meta to the ring hydroxyl substituent is preferentially deuterated, exhibiting a meta/ortho cleuteration rate of similar to 4:1. In contrast with acid-catalyzed H/D exchange and with nearly all of the reported photoactivated H/D exchange studies, the UV-induced H/D exchange of tyrosine is optimal at pH 9 and is effectively quenched at acid pH. Photochemical H/D exchange is strongly stimulated by the alpha-amino group (the aromatic hydrogens of p-cresol are far less subject to exchange) and by imidazole or phosphate buffers. On the basis of the results obtained here and on the previously identified cyclohexadienyl radical (Bussandri, A.; van Willigen, H. J. Phys. Chem. A 2002, 106, 1524-1532), we conclude that the exchange reaction involves a radical intermediate and results from two distinct roles of tyrosine: (1) as a phototransducer of light energy into solvated electrons (e(aq)(-)), and (2) as an acceptor of an electron to create a radical anion intermediate which is rapidly protonated, yielding a neutral cyclohexadienyl radical. Regeneration of the tyrosine can occur via a bimolecular redox reaction of the cyclohexadienyl and phenoxyl radicals to yield a carbocation/phenoxide pair, followed by deprotonation of the carbocation. The oxidation step is pH dependent, requiring the deprotonated form of the cyclohexadienyl radical. The H/D exchange thus results from a cyclic one-electron (Birch) reduction/protonation/reoxidation (by phenoxyl radical)/ deprotonation cycle. Consistent with these mechanistic conclusions, the aromatic hydrogens of tyrosine O-methyl ether are photochemically inert, but become labile in the presence of tyrosine at high pH. The deuteration rate of O-methyl tyrosine is lower than that of tyrosine and shows a preference for the ortho positions. This difference is proposed to result from a variation in the oxidation step, characterized by a preferential oxidation of a cyclohexadienyl resonance structure with the unpaired electron localized on the oxygen substituent.