The interaction of the radicals OH, t-BuO, Eaq, CO2 and O2 with the copper oxidase, laccase, from Polyporus, has been studied by the pulse-radiolysis technique. Each of these radicals formed transient adducts with a broad absorption maximum around 310 nm. Analysis of the optical properties and of the very fast rates of formation of these compounds shows that each radical interacts with a limited number of sites on the polypeptide part of the protein amongst R-S-S-R, histidine and aromatic residues. Interaction with the carbonyl group of some of the peptides bonds is also possible. The few target sites are probably hit simultaneously and electron transfer between these sites may also occur. In all cases, ina subsequent step, intramolecular electron transfer from the polypeptide radical adducts leads to a partial reduction of the blue type-1 Cu2+ with rates varying between 10(3) adn 10(4) s-1. Further reduction of the type-1 CU2+ occurs through a slow intermolecular reaction between two laccase radical transient adducts. In the case of CO2 and O2, this slow reduction could alternatively be due to an intermolecular reaction between laccase and CO2 or O2. The oxidation radicals OH, Br2 and (SCN)2, which formed radical adducts with fully ascorbate-reduced laccase, did not induce any type-1 copper reoxidation.