BACKGROUND: Infections and vascular disorders are the two most widely accepted probable causes of sudden hearing loss. Tumor necrosis factor alpha (TNF-alpha) is major pro-inflammatory cytokine that is thought to be important in the pathogenesis of sudden deafness. However, the functions of genetic polymorphism in this cytokine have not been throughly examined in the context of sudden deafness pathology. In an effort to discover polymorphism in genes whose variants have been implicated in sudden deafness phenotypes, we examined the genetic effects of TNF-alpha polymorphisms in Koreans with sudden deafness. METHODS: Two common single nucleotide polymorphism (SNP) in TNF-alpha gene were genotyped in a Korean sudden deafness. Ninety nine patients with sudden deafness (45 males and 54 females) were selected from Keimyung University Dongsan Medical Center. The control subjects consisted of healthy 285 males and 319 females. RESULTS: Human genomic DNA was extracted from peripheral blood sample. The SNP at position -863 C/A and -857 C/T of TNF-alpha promoter were analyzed by PCR and pyrosequencing. Genotype distribution and allele frquencies in subjects were in Hardy-Weinberg equilibrium (p>0.05). No significant association was found between TNF-alpha -863 C/A and -857 C/T polymorphism and sudden deafness. We examined whether the relation between TNF-alpha polymorphism and sudden deafness varied according to tinnitus. Statistical analysis of TNF-alpha polymorphism at -857 C/T showed that there was a significant difference between SD without tinnitus and the control in both genotype distribution (p<0.05) and allele frequency [OR (95% CI)=2.63 (1.29-5.34)], but not between SD with tinnitus. CONCLUSION: These findings suggest TNF-alpha polymorphisms at -863C/A, -857 C/T are likely to play a role in SD.