We are studying the role of sexually transmitted viruses in the development of human tumors. The persistence of herpes simplex virus, cytomegalovirus, and human papillomavirus nucleic acid sequences has been examined using cloned viral DNA sequences as probes. The relationship of the viruses to various stages in the progression of neoplasia is examined, with particular reference to the role of viral and/or cellular genes in the initiation, promotion, and maintenance of the neoplastic phenotype. The human tumors of major interest in this context are carcinomas of the cervix, vulva, and anus and Kaposi's sarcoma. The minimal fragment of HSV-2 DNA detected in cervical tumors is contained within a 656-bp sequence that can be used in transfection experiments to transform rodent cells in vitro to a malignant phenotype. However, neither this fragment nor any other is consistently retained in cervical tumors, suggesting that this viral DNA may initiate but not maintain the transformed phenotype.