Infection of the external human urogenital system with human papillomavirus has been implicated with the development of genital cancer. A modified polymerase chain reaction technique has been used to evaluate type specific deoxyribonucleic acid (DNA) sequences of unique E6 to E7 transforming regions of human papillomavirus genomes (types 6b/11, 16 and 18) in a morphological spectrum of in situ (carcinoma in situ) and invasive neoplasm of the penis. We studied 15 examples of carcinoma in situ [7 bowenoid and 8 nonbowenoid (squamoid or simplex)], 11 of invasive squamous carcinoma, 1 of verrucous carcinoma, 2 of verrucous hyperplasia, 1 of urethral adenocarcinoma and 1 solitary papilloma. Viral DNA was not detected in any of the nonbowenoid specimens of carcinoma in situ, the verrucous carcinoma, the adenocarcinoma or the papilloma of the penis. Human papillomavirus types 6b/11 and 18 specific sequences also were not detectable in any of the specimens examined. However, all 7 of the bowenoid forms of carcinoma in situ were positive for human papillomavirus type 16 DNA. The presence of human papillomavirus type 16 was also detected in 9 of 11 invasive squamous carcinomas and in both verrucous hyperplasias. Our results confirm that the bowenoid forms of intraepithelial neoplasms and most invasive squamous carcinomas contain the E6 to E7 portion of type 16 human papillomavirus genome.