Transplant recipient develop multiple cutaneous lesions. We have identified human papillomavirus (HPV) DNA in these lesions using three different techniques, namely polymerase chain reaction (PCR), in situ hybridization, and Southern blotting. By PCR, HPV DNA was detected in 43 of 62 samples: warts, actinic keratoses, Bowen's disease, and squamous cell carcinomas. Surprisingly, HPV 6/11, usually associated with mucosa, were frequently found in benign, premalignant, and malignant cutaneous lesions (30/43 cases). Some of these biopsies were simultaneously tested by in situ hybridization and/or Southern blotting. By in situ hybridization, HPV 6/11 were identified in two warts and one squamous cell carcinoma among 29 tissue specimens tested. Of the three samples examined by Southern blotting, HPV 6/11 were detected in one squamous cell carcinoma. In patients from a control population cutaneous biopsies did not exhibit HPV types 6/11 except in Bowen's disease; HPV types 1 or 2 were mainly found in benign warts. These findings suggest that in transplant recipients, HPV can lose their specificity towards mucosa or cutaneous epithelium. The significance of the presence of HPV 6/11 in skin lesions remains unknown.