A series of 131 routinely processed, paraffin-embedded biopsy specimens derived from the same number of patients with a bronchial squamous cell carcinoma were analyzed using in situ DNA-hybridization technique with a probe cocktail containing 35S-labeled human papillomavirus (HPV) DNA of types 6, 11, 16, 18, and 30. The 12 carcinomas shown to contain HPV DNA by the probe cocktail were subjected to in situ hybridization with the specific HPV DNA probes applied separately under high stringency conditions. HPV DNA could be found in 9 of these carcinomas; 2 cases contained HPV 6 DNA and 7 hybridized with HPV 16 DNA. The role of HPV in the development of bronchial squamous cell carcinoma is discussed in the light of the previously established morphologic evidence as well as the increasing number of reports on malignant transformation of the respiratory tract HPV lesions. The present findings of HPV DNA sequences provide further support to the concept of HPV as a potential causative agent of some bronchial squamous cell carcinomas, possibly acting synergistically with chemical or physical carcinogens. As in the genital tract, it seems clear that a respiratory tract infection by "low-risk" HPV types 6 and 11 by no means excludes the possibility of malignancy, so far ascribed almost exclusively to the "high-risk" type HPV 16.