The (A/G)-308 polymorphism of the tumor necrosis factor alpha gene (TNF) is associated with age-related diseases, but its influence on longevity is controversial. We genotyped for this polymorphism 747 Italian volunteers (401 women and 346 men, age 19-110 years). By applying a genetic-demographic (GD) approach we found that, in men, the survival function of allele A carriers is lower than that of noncarriers at all the ages (p =.044). After defining (by exploiting again demographic information) three age classes, we found that the frequency of men carrying the A allele decreases with age (p =.019), thus confirming the GD analysis results. The same analyses gave negative results in women. Therefore, allele A has a detrimental effect on life expectancy, and this effect is specific to men. A haplotype analysis carried out in men by screening the TNFa, TNFc, and TNFe microsatellite polymorphisms (spanning about 20 kb) confirmed the association of the TNF region with life expectancy.