The role of human papillomavirus (HPV) in the aetiology of in situ and invasive carcinoma of the genital tract is well established. In the rare disorder epidermodysplasia verruciformis (EV), in which patients develop extensive warts of unusual types and multiple cutaneous squamous cancers on light-exposed skin, current evidence suggests a probable role for a specific group of EV HPVs in the carcinogenic process. Determination of the possible role of HPV in the aetiology of non-melanoma skin cancers (NMSCs), which occur frequently in immunosuppressed organ allograft recipients, has been limited, until recently, by the lack of availability of a sensitive detection system for a wide range of cutaneous HPV types. We have used a combination of 2 sets of PCR primers to examine 68 benign and malignant tumours collected over a 12-year period from 25 renal allograft recipients. Cloning and sequencing of the PCR products were carried out to distinguish HPV DNA from cellular sequences. A combination of these techniques revealed HPV DNA in all viral warts, 65% of keratoses, 91% of intra-epidermal cancers and 91% of invasive squamous cancers. Both cutaneous and EV HPV types were detected, including 18 novel types. In 4 patients with multiple cancers, the most prevalent types were in the EV group: HPV 20, 23, 38 and 2 novel types, DL40 and DL267 (related to HPV 10 and 38, respectively). These 5 HPV types were present in a total of 73% of all malignant lesions tested. The technique described represents a reliable method of HPV DNA detection in NMSC. The EV group of HPVs predominate in the cancers, but the multiplicity of HPV types detected with double infection in some lesions suggests virus/virus in addition to virus/host interaction in the carcinogenic process.