There has been an explosion of knowledge pertaining to the generation and behavior of partially reduced oxygen metabolites--oxygen free radicals--in aqueous, in vitro systems; lacking is correlation of these intriguing findings to the biologically intact whole animal. Methodologies to study in vivo free radical-mediated processes are improving with the use of electron spin trapping of tissue samples, and in the future the precise role of oxygen radicals in oxygen injury may become clearer. With this new work with the chemistry and biochemistry of oxygen radicals, it is crucial to remember the special attributes of oxygen radical behavior in eukaryotic cells. There are many disparate compartments in cells that differ with respect to hydrophobicity, pH, and presence of iron salts and antioxidants. The ability of any oxygen radical; O2-, H2O2, .OH, to cause damage, will depend greatly on these and other factors. The final piece of the oxygen toxicity puzzle is the presence and activity of antioxidant substances, both enzymatic and nonenzymatic. Here again, compartmentalization is important. To provide beneficial protection, the antioxidant must be present in sufficiently high concentrations at the site of radical production or damage. In the special case of the premature infant who requires oxygen therapy, the balance between oxygen radical production and antioxidant capacities will determine whether oxygen injury ultimately occurs. The biologic uniqueness of the premature infant in regards to maturation and growth mandates investigations of these biochemical phenomena in appropriate experimental models, rather than extrapolation from studies conducted in adults and perhaps even full-term newborns.