Of 4 patients who underwent cystourethroscopy, biopsy and laser excision of suspected urethral condylomata acuminata 3 had coexistent grade I papillary transitional cell carcinoma of the urethra. Human papillomavirus type 6 messenger ribonucleic acid was demonstrated within biopsy specimens using tritium-labeled single-stranded antisense ribonucleic acid probes. Compared to condylomata the papillary transitional epithelium expressed less viral message, which might be expected in an epithelium that does not show full squamous epithelial or koilocytotic differentiation. Among these patients there was 1 papillary transitional lesion in the bladder that, although histologically similar, did not express human papillomavirus message, suggesting differential susceptibility of epithelium between the bladder and urethra. The finding of active human papillomavirus transcription within the urethral papillary transitional lesions raises the possibility of an active role for the virus in the pathogenesis of these lesions. These findings broaden the spectrum of epithelial types reported to support human papillomaviruses and provides impetus for a wider search for these viruses in other transitional cell neoplasms.