The effects of chronic lithium co-therapy on the expression of gentamicin and amikacin ototoxicity were tested in guinea-pigs. Intramuscular injection of different doses of gentamicin (5, 10 mg/kg/day) and amikacin (150, 300 mg/kg/day) for three weeks, induced hearing loss consistent with the established pattern of aminoglycoside ototoxicity. Lithium salts remains one of the most widely used treatment for depressive illness. Administration of lithium chloride (600 mg/l, 35 days) in drinking water changed auditory brainstem response in a time-dependent manner. Pretreatment of animals with lithium chloride after seven days induced significant alterations in wave latency and interval. The present study assesses the protective effects of chronic lithium on gentamicin-induced ototoxicity in guinea pig. The results suggest that duration of lithium administration may be involved in auditory brainstem response changes and the observations could be accounted for, at least partially, by lithium- and aminoglycosides-induced perturbations of the phosphoinositide cascade within the inner ear.