The p53 gene has been implicated in the pathogenesis of lung cancer as a tumor suppressor gene. Aberrations of the p53 gene (exon 6-8) was examined in 34 surgical specimens of lung cancer with single-strand-conformation-polymorphism analysis of polymerase chain reaction products. Structural abnormalities of the p53 gene were observed in 30 tumor specimens (88.2%), i.e, in 10 of the 12 specimens with squamous cell carcinoma, 8 of the 10 with adenocarcinoma, all the 3 small cell carcinoma, the only one large cell carcinoma, all the 5 alveolar cell carcinoma and all the 3 adenosquamous carcinoma. The aberrations of the p53 gene were not limited to a particular histological type or clinical stage and were not associated with degree of differentiation or history of heavy smoking. It is suggested that high mutation rate of the p53 gene may participate in the genesis of lung cancer. In this study, multiple primer polymerase chain reaction method was applied to detect the human papillomavirus DNA (HPV DNA) in human lung cancer. Only 4 of these 34 specimens were HPV DNA positive, and they were all of squamous cell carcinoma, 3 of them had p53 mutation.