The authors report a case of primary urethral carcinoma which seems to be linked to human papillomavirus (HPV) infection. Southern blot hybridization of phosphorus 32 (32P)-labeled DNA extracted from the cancer tissue gave a positive reaction with HPV-6. Specimens of the tumor material subjected to in situ hybridization with 3H-labeled HPV-6 DNA showed numerous tumor cell clusters with clearly labeled nuclei. Using immunoperoxidase staining the authors found papillomavirus structural antigen within cell nuclei of the tumor tissue.