The exposure of red cells to phototherapy light in the presence of a sensitizer (bilirubin) resulted in oxidative injury to the red cell membrane as manifested by a significant increase in the concentration of the products of lipid peroxidation (TBA reactants and diene conjugation) in the membrane and hemolysis. To induce a photo-oxidized membrane injury, the sensitizer (bilirubin) has to be membrane bound. Thus, by altering the availability of free bilirubin in the red cell suspension through changes in the molar concentration ratio of bilirubin to albumin, one is able to regulate the occurrence and extent of the oxidative red cell membrane injury. The clinical implications of these findings are discussed.