Abstract Our laboratory has focused on understanding the mechanisms controlling acellular Hbs oxidative and nitrosafive toxicities in vitro and in vivo. Evidence is accumulating which suggests that reduction-oxidation redox reactions of free Hb and hemoglobin-based oxygen carriers (HBOCs), also known as blood substitutes do occur in vivo with some potentially serious clinical consequences. A primary focus of the research is based on the role of oxidants-mediated changes in acellular Hb under conditions that can mimic ischemia/reperfusion injury. Depending on whether host endogenous reductive mechanisms are employed or not, we will invesfigate Hb oxidative reactions in vivo using rats (ascorbate producing) or guinea pigs (ascorbate non-producing). The role of haptoglobin (Hp) and/or other antioxidant materials in supplemenfing endogenous antioxidant mechanisms will be invesfigated. For the investigation of effects of oxygen carrying HBOCs on cardiac