Age-related cochlear structural changes include the degeneration of sensory, neural cells and the stria vascularis. The hypothesis that cellular degeneration results from exposure to oxidative products of respiration was tested by supplementing aged dogs with a diet high in antioxidants and mitochondrial metabolites and by genetically modifying the expression level of the antioxidant, manganese superoxide dismutase (SOD2) in mice. Aged dogs received either a high antioxidant diet or a normal, control diet for the last 3 years of their life. Cellular measures were compared among the two aged groups (10-15 years) and young dogs. Both aged groups had cellular degeneration relative to young dogs, but the animals fed the antioxidant diet showed less degeneration at the base and apex than the control-diet group. Transgenic mice, heterozygous null for SOD2, produce only half as much enzyme as a normal mouse. These mice showed no increase in the amount of hearing loss relative to the background strain. A diet containing antioxidants reduced the magnitude of cochlear degeneration. Genetic reduction of one antioxidant, however, did not increase the magnitude of hearing loss in aging mice. A reduction in one enzyme seems to be compensated while the addition of a complex of factors is effective.