Renal allograft recipients (RARs) have a well-documented increased incidence of viral warts and cutaneous neoplasia, particularly those with long graft life and high sun exposure. A clinicopathological survey of 69 RARs in south-east Scotland, with follow-up periods of up to 28 years after transplantation, revealed marked variation in patient susceptibility to cutaneous malignancy with concomitant variation in HPV prevalence. Skin cancers were found in 34 patients. Eight patients showed high susceptibility [defined as more than four intraepidermal carcinomas (IECs) or invasive squamous cell carcinomas (SCCs)] 42 had intermediate susceptibility (1-3 IECs or SCCs, or >3 keratoses) and 18 had low susceptibility (< or = 3 keratoses and no cancers). SCCs, IECs and keratoses from the high-susceptibility group were found to have greater prevalences of human papillomavirus (HPV) DNA (56%, 45% and 50% respectively), than SCCs (0%) and IECs (33%) from intermediate-susceptibility RARs and keratoses (36%) from the combined intermediate- and low-susceptibility groups and compared with a group of immunocompetent controls (27%, 20% and 15% respectively). No differences in p53 protein accumulation, determined immunohistochemically, were observed in tumours from the three groups. Categorization of RARs by susceptibility to cutaneous malignancy provides clinically useful information, as significantly more high-susceptibility patients (38%) developed aggressive, potentially lethal anogenital or cutaneous squamous cell cancers than did patients in the intermediate group (5%, P=0.005) or the low-susceptibility group (0%).