The ototoxic potentials of two aminoglycoside antibiotics, amikacin and gentamicin, were compared in cats, using several otoxicity assessment techniques. Daily subcutaneous doses of 90 and 45 mg of amikacin per kg and 18 and 9 mg of gentamicin per kg (approximately six and three times the daily human dose) were administered to cats for extended periods of time until cochlear or vestibular dysfunction developed. Renal tissue damage and serum and perilymph antibiotic concentrations were also monitored. Amikacin selectively produced an impairment of cochlear function after an approximate cumulative dose of 3,600 mg/kg obtained after 41 days at 90 mg/kg per day or 78 days at 45 mg/kg per day, as determined by electrophysiological assessment. Gentamicin caused an impairment of vestibular function after an approximate cumulative dose of 700 mg/kg obtained after 42 days at 18 mg/kg per day or 68 days at 9 mg/kg per day, as determined by ataxia and impaired righting reflex. Gentamicin also moderately reduced electrophysiological cochlear responses and appeared to cause histological renal tissue change more frequently than did amikacin.