Alzheimer's disease (AD) is one of most common chronic neurodegenerative diseases in the elderly. Tumor necrosis factor-alpha (TNF-alpha) was found elevated markedly in the serum and the cerebral spinal fluid of AD patients. And the elevation of TNF-alpha was thought to be associated with the occurrence of AD in China. However, it is still unclear whether the TNF-alpha polymorphism is related to the sporadic Alzheimer's disease (SAD) in China as well. Hence, in this study, we try to investigate the relationship between TNF-alpha G-308A polymorphism and its susceptibility to SAD in a Southern China population. The polymerase chain reaction-sequence specific primers (PCR-SSP) was performed to detect the frequencies of genotypes and alleles of TNF-alpha in 112 SAD patients and 121 controls. And the levels of TNF-alpha in serum were measured by radioimmunoassay. The differences of polymorphic distribution and the levels of TNF-alpha in serum between groups were then analyzed, and odds ratio was computed for association analysis. The frequency of A-allele was significantly increased in patients with SAD compared with that of the controls (chi(2)=4.256, P=0.039). A significantly increased risk of SAD was observed in the carriers of A-allele (OR=2.635, 95% CI 1.027-6.763, P<0.01). In parallel, the serum level of TNF-alpha in SAD group was much higher than that in control group (chi(2)=10.21, P=0.0042). And the elevation of serum level of TNF-alpha was closely associated with the risk of SAD (OR=3.542, 95% CI 2.304-8.854, P<0.05) as well. These results suggested that the TNF-alpha gene G-308A polymorphism might be a risk factor for SAD in Southern China. A-allele might play a role in the susceptibility of SAD.