The reactions between aqueous ClO2 and guanosine 5'-monophosphate (5'-GMP) are investigated from pH 5.96 to 8.30. The decay of ClO2 follows mixed first-order and second-order kinetics. The addition of chlorite (0.01-0.05 M) to the reaction mixture suppresses the reaction rate and changes the observed decay of ClO2 to second-order. The reaction rates increase greatly with pH to give oxidized products. The second-order rate constant for the guanosine anion is 4.7 x 10(5 )M-1 s-1 and comprises a mixture of rate constants, k1k2/k-1. The ratio k1/k-1, with a calculated value of 2.4 x 10(-4), corresponds to the reversible reaction between ClO2 and the guanosine anion to generate ClO2- and the guanosyl radical. To determine k1/k-1 and k2, E values for guanosine and ClO2 are used as well as acid dissociation constants for guanosine and its radical. The value of k1 (1.1 x 10(5) M-1 s-1) represents the reaction between ClO2 and the guanosine anion as determined by initial rates. The second-order rate constant k2, with a value of 1.8 x 10(9 )M-1 s-1, represents the reaction between the guanosyl radical with a second molecule of ClO2 to generate a guanosyl-OClO adduct. The consumption of two mol of ClO2 per mol of 5'-GMP corresponds to a four-electron oxidation that gives ClO(2- )in the first step and HOCl in the second step. The 2',3',5'-tri-O-acetylated derivative of guanosine is used to more easily separate guanosine from its ClO2 oxidation products. Imidazolone and monochlorinated imidazolone are identified as products of the reaction between ClO2 and guanosine.