The aim of this study was to investigate papillomavirus (HPV)-DNA in precancer and cancer of the cervix, vulva, and endometrium by in situ/dot blot/Southern blot hybridization and polymerase chain reaction (PCR). Myc/erbB-2 expression was examined by Northern blot analysis. PCR was the most sensitive HPV detection method, demonstrating HPV-DNA in all pre-invasive and invasive cervical lesions (n = 21) and most (3 of 4) vulvar carcinomas in contrast to an overall rate of 60% with other techniques. Particular phenotypes (adenoid cystic/basal cell carcinoma of the vulva, cervical adenocarcinoma) were found to contain HPV. Endometrium harboured HPV not only in two cases of cervical cancer, but also in 3 of 8 primary endometrial carcinomas and 3 of 8 non-malignant conditions. Myc activation was confined to three squamous cell carcinomas, most markedly in one HPV-6-positive verrucous variant. ErbB-2 over-expression was only seen in one HPV-18 infected advanced endometrial tumour. Our findings point to a range of HPV-infected lesions broader than previously supposed and possible contributions of HPV-independent molecular events to carcinogenesis in this field.