The uncommon allele (TNF2) of a polymorphism in the promoter region of the tumor necrosis factor-alpha (TNF-alpha) gene has been reported to be increased in Caucasian systemic lupus erythematosus (SLE) patients (associated with HLA-DR3). To investigate whether TNF2 contributes towards susceptibility to Chinese SLE patients (not associated with HLA-DR3), 100 patients with SLE and 107 controls were studied. The frequency of TNF2 allele in controls was 0.140. There was a strong association between TNF2 allele and HLA-DR3 (P < 10(-8)) in controls. The frequency of TNF2 allele in SLE patients was 0.15. There was no difference in frequencies of TNF2 allele between patients and controls. This finding strongly suggests that TNF2 does not play a direct role in the susceptibility of SLE.