Polymorphonuclear leukocytes and other inflammatory cells on exposure to appropriate stimuli release superoxide anion radical into the extracellular space. This results in the further generation of other activated oxygen species such as hydrogen peroxide, hydroxyl radical and singlet oxygen. We have assessed the influence of activated oxygen species, generated by substrate-xanthine oxidase systems, on the degradation of hyaluronic acid, human glial cells in culture and the microcirculation of the hamster cheek pouch. Hyaluronic acid degradation was observed and morphological changes, culminating in cell death, were seen in glial cells. Increased microvascular permeability and increased polymorphonuclear leukocyte-endothelial adhesion were also observed. The results suggest that a variety of alterations to macromolecular and cellular elements of tissues can be mediated by specific free radical species. Similar mechanisms may play a role in the structural and cellular injury occurring in the microcirculation during inflammation and other disease processes.