It is being reported that human papillomavirus (HPV) has been implicated in the pathogenesis of various neoplastic lesions of the genital organs. To investigate the etiological role of HPV and its types in nasolaryngeal papillomas, we retrospectively analyzed HPV genomes by nucleic acid hybridization methods; for detecting DNA and mRNA, we employed the recently developed nonradioactive (digoxigenin labeled) DNA probes and compared the results by radioisotope methods. In total, 43 cases of papillomatous lesions were examined. They were verruca vulgaris of the nasal vestibule (Nr = 2), nasal inverted papilloma (IP, Nr = 26), and laryngeal papilloma (Nr = 15). HPV types examined were type 2, 6, 11, 16 and 18. Two cases of verruca vulgaris were shown to contain HPV-2 DNA and its mRNA by in situ hybridization. HPV-11 DNA was detected in 3 cases (12%) of nasal inverted papilloma whereas HPV-16 was detected in 1 case (4%); the latter case was associated with squamous cell carcinoma. These results suggest that HPV may be implicated in the development of IP, and HPV-16 may play an important role in the malignant transformation of IP. In the cases of multiple laryngeal papilloma (Nr = 8, one juvenile type and 7 adult type), either HPV-6 or HPV-11 was detected at the high rate (6/8, 75%). The presence of the HPV genomes provides strong evidence for the HPV etiology of these laryngeal papillomas. Whereas in the cases of adult single laryngeal papilloma (Nr = 7), HPV was not detected. Technically, the sensitivity of digoxigenin (DIG) labeled DNA probe was almost same as 35S labeled probe by dot blot hybridization, thus we applied DIG labeled probe to Southern blot hybridization with low background. By in situ hybridization using digoxigenin labeled probes, the rates of HPV detection were almost equal to those by 35S labeled probes.(ABSTRACT TRUNCATED AT 250 WORDS)