With respect to both permeability and inactivation of membranous GAPDH, ghosts were more susceptible than erythrocytes to free radicals produced in the gamma-irradiation of aqueous solutions. The rate of increase in the permeability of irradiated ghosts was immeasurably greater than that of irradiated erythrocytes, while the rate of inactivation of GAPDH was 21-fold greater. The sensitivity of ghosts to radiation damage was affected strongly by the presence of oxygen during irradiation. In the presence of air, the rates of increase of permeability and inactivation of GAPDH were 2.8- and 1.5-fold of those in the presence of N2. The use of buffer saturated with oxygen accelerated the aerobic rates of increase of permeability and inactivation of GAPDH by 60- and 2.7-fold. These results indicate that inactivation of GAPDH is somewhat sensitive to oxygen, particularly at high concentration of oxygen. Nevertheless, in air or under nitrogen, the rate of enzymic inactivation was almost an order of magnitude greater than that of increase of permeability, indicating that the former is much more sensitive to irradiation. The major mechanism of the oxygen effect observed is the ability of oxygen to increase the branching of the free radical chain reactions which propagate damage after initiation within the membrane.