Papillomavirus-related genital neoplasms are one area where molecular biology has had an impact at many levels. Studies of cell transformation, gene expression, and genome organization have linked papillomaviruses to neoplasia; they have also provided data suggesting potential pathways by which the papillomaviral genome exerts its effect on cells. Molecular epidemiological studies using clinical material have identified specific HPV types with neoplasia, profiled the populations at risk for these infections, and supported the emerging concept of latent infection. Studies using in situ hybridization have confirmed the close relationship of neoplastic change with certain infections (such as HPV-16), and have detailed the transcription patterns of the papillomavirus genome in warts, precancers, and carcinomas. The technology of in situ hybridization has facilitated the evaluation of archive material; using this material, the close relationship between HPV type 18 and adenocarcinomas and small-cell carcinomas has been described. Methods for expressing HPV proteins in bacteria have produced a spectrum of antisera to specific gene products, which in turn will facilitate mapping their distribution in tissues, determining their biological significance, and clarifying the host immune response to genital papillomavirus infections. Although these multidisciplinary approaches help to promote an understanding of genital HPV infections and their related neoplasms as well as clarifying the role of HPV in the evolution of genital neoplasia, the clinical utility of this information has not yet been established.