Recently published data have suggested a link between active human papillomavirus (HPV) infection and the development of bladder cancer. This study was undertaken to test for HPV genomic material in the tumors of patients without evidence of ongoing viral infection. Twenty-three consecutive patients with clinical evidence of intravesical neoplasia and no history of HPV infection or clinical evidence of intercurrent disease, underwent cystopanendoscopy and biopsy as part of the routine evaluation and treatment of their tumor. Routine pathologic evaluation and southern blot analysis of biopsy material were done to establish the presence or absence of HPV DNA in the bladder tumors. Twenty-one tumors were identified by routine histology: 20 were low-to-moderate grade transitional cell carcinomas; 1 was found to be squamous cell carcinoma; 1 patient had moderate dysplasia; and 1 patient had evidence of inflammation. Four of the 20 transitional cell tumors (20%) were found to contain HPV DNA. In addition, the patients with dysplasia and cystitis were also shown to have HPV genomic material in their biopsy specimens. Viral types 6/11, 16/18, and 31/33 were found. The 20 percent incidence of HPV genomic material in bladder tumors from patients without clinical evidence of viral infection is in keeping with the observations of other investigators. We present the implication of these findings within the context of our current understanding of viral oncogenesis in the urinary bladder.