Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine that is thought to play a role in the pathogenesis of periodontal disease. TNF-alpha production is regulated by many factors, including certain alleles of TNF gene polymorphisms. In the present study, TNF genotypes of 3 bi-allelic polymorphisms were determined in 32 Caucasian patients with adult periodontitis and 32 orally-healthy matched controls, and correlated with TNF-alpha production by oral polymorphonuclear leukocytes (PMN). No differences in distribution of TNF alleles of the -238, -308, or +252 gene polymorphisms were observed between patients and controls or between patients with different disease severity. However, the level of TNF-alpha production by oral PMN correlated with the TNF-alpha 308 genotype in patients with adult periodontitis, with increased production found in patients with the T1,2 genotype (t-test; P=0.037). When cytokine production was examined in patients according to disease severity, an association between the T1,2 genotype and increased production was observed only in patients with advanced disease (t-test; P=0.05). These findings suggest that further studies are warranted to determine if the TNF genotype is a risk factor for severity of disease in adult periodontitis.