Tumor necrosis factor-alpha (TNF-alpha) mediates alcohol-induced organ dysfunction, including alcoholic hepatitis. Variations in the TNF-alpha gene may underlie the individual predisposition to alcoholic liver disease. Measurement of serum TNF-alpha levels has become a routine in clinical practice. The study was aimed at investigating the level of serum TNF-alpha levels in adults and analyzing its relationship with different levels of alcohol consumption, as well as the potential interaction between alcohol consumption and common TNF-alpha gene polymorphisms in relation to TNF-alpha levels and liver disease. Serum TNF-alpha was measured in a random sample of 459 individuals from a general adult population and in 137 hospital-admitted alcoholics. Three common TNF-alpha gene polymorphisms (-238G> A, -308G> A, and -857C> T) were investigated in 419 of these individuals. In the general adult population, the TNF-alpha levels were similar in alcohol abstainers and alcohol drinkers. Alcoholics admitted to the hospital showed the highest TNF-alpha levels, which were correlated with liver dysfunction. We found no evidence of an interaction between alcohol consumption and TNF-alpha gene polymorphisms in relation to TNF-alpha levels. Carriers of the TNF -238A allele tended to have a higher prevalence of advanced liver disease than -238G homozygotes, confirming previous reports. In conclusion, light-to-moderate drinking had no significant effect on the levels of serum TNF-alpha levels. Serum TNF-alpha levels are elevated in alcoholics independently of common TNF gene polymorphisms.