The mechanism of hearing loss due to the administration of intravenous erythromycin was investigated in the albino guinea pig, and it was found for the first time that this drug causes cochlear dysfunction. The endocochlear potential (EP) and the cochlear microphonics (CM) recorded at the first cochlear turn transiently decreased when erythromycin was administered intravenously at dosages of 100 and 150 mg/kg. The averaged maximum decrease in EP was 16 mV (n = 5) and 33 mV (n = 5) for 100 and 150 mg/kg, respectively. The maximum decrease in the CM was about 25% when the EP reached its lowest value with the injection of 150 mg/kg. A complete recovery of the EP and CM ensured within 20 minutes after each erythromycin dose. The perilymphatic perfusion of 3 mmol/L of erythromycin decreased the EP and CM; however, in contrast to the intravenous administration, the decrease of the CM was nearly complete and both the EP and CM were irreversible. Hearing loss due to intravenously administered erythromycin could likely be attributle to the transient dysfunction of the stria vascularis, although concomitant dysfunction of the central auditory pathway cannot be excluded.