The most important electron acceptor in the biosphere is molecular oxygen which, by virtue of its bi-radical nature, readily accepts unpaired electrons to give rise to a series of partially reduced species collectively known as reduced (or ‘reactive’) oxygen species (ROS). These include superoxide (O^·-₂), hydrogen peroxide (H₂O₂), hydroxyl radical (HO^·) and peroxyl (ROO^·) and alkoxyl (RO^·) radicals which may be involved in the initiation and propagation of free radical chain reactions and which are potentially highly damaging to cells. Mechanisms have evolved to restrict and control such processes, partly by compartmentation, and partly by antioxidant defences such as chain-breaking antioxidant compounds capable forming stable free radicals (e.g. ascorbate, α-tocopherol) and the evolution of enzyme systems (e.g. superoxide dismutase, catalase, peroxidases) that diminish the intracellular concentration of the ROS. Although some ROS perform useful functions, the production of ROS exceeding the ability of the organism to mount an antioxidant defence results in oxidative stress and the ensuing tissue damage may be involved in certain disease processes. Evidence that ROS are involved in primary pathological mechanisms is a feature mainly of extraneous physical or chemical perturbations of which radiation is perhaps the major contributor. One of the important radiation-induced free-radical species is the hydroxyl radical which indiscriminately attacks neighbouring molecules often at near diffusion-controlled rates. Hydroxyl radicals are generated by ionizing radiation either directly by oxidation of water, or indirectly by the formation of secondary partially ROS. These may be subsequently converted to hydroxyl radicals by further reduction (‘activation’) by metabolic processes in the cell. Secondary radiation injury is therefore influenced by the cellular antioxidant status and the amount and availability of activating mechanisms. The biological response to radiation may be modulated by alterations in factors affecting these secondary mechanisms of cellular injury.