The concept of genetic factors playing a role in the pathogenesis of lung cancer has gained increased attention. The present study was undertaken to reexamine the question of HLA antigen association with carcinoma of the lung. In a study of 90 patients, a significant association occurred between HLA-DR7 and resistance to lung cancer, after accounting for smoking status and sex. HLA class I antigens were also implicated. These results suggest that major histocompatibility complex loci affect carcinoma of the lung.