Twin concordance studies suggest that genetic factors play a role in determining why only a minority of heavy drinkers develop hepatitis and cirrhosis. Tumor necrosis factor α (TNF-α) has emerged as the “final common pathway” in the pathogenesis of alcohol-related hepatic necro-inflammation. We have examined the frequency of the two recently described polymorphisms of the TNF-α promoter in 150 patients with biopsy-proven alcoholic liver disease and 145 healthy volunteers. There was a significant excess of the rare allele (TNFA-A; G(−238) → A) at position −238 in patients with steatohepatitis compared with controls or patients without this lesion. This is consistent with previous suggestions that the TNFA-A allele, which falls within a putative Y regulation box of the TNF-α promoter, is associated with increased TNF-α expression. No differences were observed for the polymorphism at position −308.