In order to study the role of human papillomavirus (HPV) in genital cancer, we attempt to determine the presence of HPV in tumors of the genital tract. In the current study, we have examined 35 histologically diagnosed cases of vulvar lesions in attempts to compare the sensitivities of various methods of detecting HPV. All but 7 vulvar lesions contained HPV DNA by Southern blot DNA hybridization. Detectability of HPV by immunocytochemistry and koilocytosis significantly declined as compared to DNA hybridization. The detection of HPV DNA by in situ hybridization is discussed.