Objectives: To determine the etiology of adult-onset sensorineural hearing loss when there is no obvious cause by history and physical examination. Methods: A total of 60 adult subjects with bilateral sensorineural hearing loss of no obvious etiology by history and physical examination underwent evaluation by high-resolution computed tomography of the temporal bone, autoimmune panel, and DNA testing for mutations of both the connexin 26 gene and mitochondrial DNA (1555A>G and 7445A>G). Results: An etiologic diagnosis was reached in 4 instances: cochlear otosclerosis in 1 case, and 3 cases of mitochondrial DNA 7445A>G mutation. Conclusions: This result underscores the importance of an etiologic search during the evaluation of adults with sensorineural hearing loss of no obvious cause, as there are medical therapies available to slow down the hearing impairment caused by cochlear otosclerosis and by the mitochondrial DNA 7445A>G mutation.