Hearing loss, isolated or syndromic, is the most frequent sensory deficit in humans. Many nuclear genes for deafness have been identified but there is now ample evidence that sensorineural hearing loss (SNHL) also can be associated with mitochondrial DNA (mtDNA) mutations and transmitted maternally. SNHL is a common feature in patients with the MELAS syndrome(mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) and a mtDNA mutation at nt 3243. This same mutation can also present with diabetes and SNHL in some patients and SNHL is often the sole feature in some relatives of MELAS patients. Aminoglycoside-induced deafness (AID) is associated with a mutation at nt 1555 and a mutation at 7445 was reported in a family with only SNHL. The aim of our study is to establish the prevalence of described mtDNA mutations in patients with SNHL. Identification of individuals with these mutations is important for genetic counseling and identification of other family members at risk for MELAS or AID. Patients were recruited from the ENT clinic at a University-affiliated facility. Selection was based upon the presence of severe to profound bilateral hearing loss of prelingual or childhood onset. An epidemiologic questionnaire and a detailed pedigree was obtained for each patient. DNA was extracted from peripheral blood and analysis for mtDNA mutations at nt1555, 3243, and 7445 performed using PCR/RFLP -based methods. Even though a number of our patient families had clinical features suggestive of a mtDNA mutation (21 were consistent with maternal inheritance, 17 received parenteral antibiotics, and 32 have relatives with diabetes) none of the 56 patients screened thus far had any of the three candidate mtDNA mutations. We plan to test additional patients and to analyze select patients with suggestive histories for previously undescribed mtDNA mutations in relevant regions of mtDNA, such as tRNALeu(UUR),and 12s rRNA.