HO. attack on hyaluronic acid, related polymers and monomers has been studied by both direct, rapid-flow, EPR (ESR) and EPR spin trapping using a variety of traps. Evidence has been obtained, with the monomers, for essentially random hydrogen-atom abstraction at all the ring C -- H bonds with glucuronic acid, and at all sites except the N-acetyl side chain and C(2) with N-acetylglucosamine. The initial radicals do not undergo rapid rearrangement reactions at pH 4; however at both lower and higher pH values, acid- and base-catalysed rearrangement process, respectively, result in the loss of these species. The rate of loss of these species is dependent on the substrate, with those derived from N-acetylglucosamine undergoing slowed acid-catalysed rearrangement than the glucuronic acid-derived species. This is rationalised in terms of a rearrangement reaction of 1.2-dihydroxyalkyl(1.2-dio) radicals involving an electron-deficient radical-cation intermediate; the formation of this species would be disfavoured by the electron-withdrawing N-acetyl substituent. The base-catalysed process, which is believed to involve a radical-anion intermediate, occurs rapidly at pH 7.4, and appears to be less substrate dependent. In the case of glucuronic acid- (but not N-acetylglucosamine-) derived species this latter process results in the detection of ring-opened semidione species. With equimolar mixtures of the two monomers essentially random attack occurs on the two rings. However with chondroitin sulphate A, attack appears to be much more selective, with a radical generated at C(5) on the glucuronic acid ring present at highest concentration. The initial radicals obtained with this polysaccharide also undergo base- and acid-catalysed rearrangements; this leads to strand-breakage and the formation of low-molecular-weight material. Spin-trapping experiments carried out with hyaluronic acid, and a number of other polysaccharides, resulted in the detection of a number of novel spin adducts, the formation of which are consistent with attack on both the sugar rings in the polymer. The pH dependence of the observed spectra, and the detection of additional species at some pH values, suggest that at least some of the initial radicals undergo base-catalysed rearrangement reactions which result in strand-breakage and the formation of low-molecular-weight fragments. The extent of fragmentation at a particular pH, is also affected by the radical flux, with high radical yields giving more low-molecular-weight material. These observations suggest that pH-independent processes also contribute to strand-cleavage; this may be due to beta-cleavage of the radicals formed at C(1) on either ring, C(3) on N-acetylglucosamine or C(4) on the glucuronic acid ring.