High-level noise has the capability of damaging the cochlea via several mechanisms, including the generation of reactive oxygen intermediaries with their capacity of cytotoxicity. Several laboratories have reported that prior exposure to conditioning noise (moderate levels of noise for several days) can render the cochlea more resistant to future traumatic exposures. This lab in collaboration with the Albert Einstein College of Medicine, reported that antioxidant enzymes: catalase, glutathione reductase, and (gamma)-glutamyl cysteine synthtase, are upregulated with noise exposure---the greatest increase being found in animals exposed to a traumatic noise with previous conditioning noise exposure. This increase, with conditioning noise, suggests the antioxidant system may be involved in protection from noise exposures. To better understand the role of antioxidants, a second set of experiments was conducted that manipulated their level. The applications of R-N6-phenylisopropyladenoisine (R-PIA) (a drug that upregulates the antioxidant system) decreases the effects of noise; and conversely, applications of buthione-sulfoximine (a drug that suppresses the antioxidant system) increases the effects of noise. These results will be discussed in terms of the balance of free radicals/antioxidants as a common factor in noise and other ototoxic reactions. Also, the R-PIA studies will be discussed in terms of potential therapeutic value.