Cyanide-sensitive superoxide dismutase (SOD) activity in rabbit epididymal spermatozoa decreases with time of aerobic incubation of a washed cell suspension. The inactivation of SOD activity correlates linearly with the increasing percent immotile sperm observed under these conditions. A linear correlation was previously shown between percent immotile sperm and spontaneous lipid peroxidation in both high Na+ and high K+ media, the peroxidation rate being 8-fold higher in the high K+ medium as compared to the high Na+ medium. These 2 linear correlations connect SOD inactivation and lipid peroxidation. The reaction of .**GRAPHIC**. with the sperm cells was characterized by a 2nd order rate constant ks. The value of ks for fresh cells is 1.2 .times. 10-8 (cells/ml)-1 min-1 in high Na+ medium and 12.5 .times. 10-8 (cells/ml)-1 min-1 in high K+ medium. This difference is reflected in the lipid peroxidation rate in the 2 media. As SOD is inactivated during aerobic incubation in the high Na+ medium, the value of ks increases to 18.3 .times. 10-8 (cells/ml)-1 min-1 corresponding to 100% inactivation of SOD. This value is close to that of 19.9 .times. 108 (cells/ml)-1 min-1 obtained in the high Na+ medium and 22.9 .times. 108 (cells/ml)-1 min-1 obtained in the high K+ medium with fresh cells in the presence of Cn- to inactivate the SOD. Attack of .**GRAPHIC**. to induce lipid peroxidation in fresh cells may occur at the plasma membrane and is sensitive to the ionic composition of the medium, but as SOD becomes inactivated during aerobic incubation, more intracellular lipid peroxidation occurs, which is not affected by the ionic composition of the medium. SOD activity could be the primary enzymic defense against oxidative degradation available to rabbit spermatozoa.