Extracellular matrix molecules, such as collagens, are good targets for oxygen free radicals. Collagen is the only protein susceptible to fragmentation by superoxide anion as demonstrated by the liberation of small 4-hydroxyproline-containing-peptides. It seems likely that hydroxyl radicals in the presence of oxygen cleave collagen into small peptides, and the cleavage seems to be specific to proline or 4-hydroxyproline residues. Hydroxyl radicals in the absence of oxygen or hypochlorous acid do not induce fragmentation of collagen molecules, but they trigger a polymerization of collagen through the formation of new cross-links such as dityrosine or disulfure bridges. Moreover, these cross-links can not explain the totality of high molecular weight components generated under these experimental conditions, and the nature of new cross-links induced by hydroxyl radicals or hypochlorous acid remains unclear.