Tumor necrosis factor alpha (TNF alpha) and lymphotoxin (TNF beta) are cytokines with numerous similar immunoregulatory effects. In pulmonary fibrosis, TNF alpha/beta appears to play a critical role in the regulation of the fibroproliferative response. The human TNF alpha/beta genes are located between the HLA-B and the HLA-DR region. In man 5.5 kb and 10.5 kb of TNF alpha/beta restriction fragment length polymorphic (RFLP) bands have recently been identified by means of enzyme NcoI. TNF alpha/beta production is reported to be correlated to the NcoI RFLP. In some collagen diseases, a decreasing frequency of the 10.5 kb band is reported. The two allele NcoI RFLP of the TNF alpha region, yielding bands of 5.5 kb and 10.5 kb, was investigated in normal Japanese subjects and patients with IIP. The frequency of these bands was not different between normal subjects and patients with IIP. However, in female patients, the frequency of the 5.5 kb band was significantly increased compared with those in the male patients and normal subjects. The increase of this band may have some relation to the pathogenesis of idiopathic interstitial pneumonia.