Using blot hybridization, we analyzed 10 bladder tumors (1 transitional cell carcinoma in situ, 1 adenocarcinoma, and 8 papillary tumors) for the presence of human papillomavirus (HPV) DNA. We detected HPV 16 DNA in a transitional cell carcinoma in situ, whereas no HPV DNA was found in the other bladder tumors. The patient, a 40-year-old female, who harbored HPV 16 DNA in the bladder tumor, had mild immunodeficiency and recently suffered from the bladder tumor, common warts on the right hand, Bowen's disease of the vulva, and severe dysplasia of the vaginal wall. From each of these lesions, we detected the DNA of HPV 16 or an unclassified HPV. HPV DNAs existed in nonintegrated form in all lesions examined. To our knowledge, this is the first case in which a bladder tumor was shown to harbor HPV DNA. However, HPV does not seem to be regularly present in bladder tumor, because we could not detect HPV DNA from the most common bladder tumor, i.e., papillary tumor. Our demonstration of HPV 16 DNA in a transitional cell carcinoma in situ of the bladder suggests that HPV may be associated with some of the bladder tumors of this type.