Recent studies on oxyradicals associated with ischemia and hypoxia have emphasized the formation of oxyradicals during the reperfusion of ischemic tissue. However, the possible role of radicals formed at reduced oxygen pressures contributing to hypoxic damage has for the most part been neglected. We have reviewed the data which suggest that free radicals are formed under hypoxic conditions and that in the presence of low oxygen pressure even oxyradicals are formed. Mechanisms to explain the dichotomy whereby low oxygen pressure can actually increase the formation of oxyradicals are discussed. Evidence is presented for a mechanism in erythrocytes associated with conformational rearrangements which take place when oxygen is dissociated from hemoglobin. It is further demonstrated that the oxyradicals released from erythrocytes under hypoxic conditions can damage fibroblasts incubated with erythrocytes. These results suggest that oxyradicals produced under hypoxic conditions can be a potential source for cellular and tissue damage.