Prostatic cancer cell cultures possessed intracellular immunofluorescent antigens specific for human cytomegalovirus (CMV) but produced no infectious virus particles. Norman human prostatic tissue yielded a CMV isolate that transformed primary human embryo lung cells in vitro. These cell transformants were highly oncogenic when transplanted to athymic nude mice. Immunological studies revealed that sera from prostatic cancer patients reacted significantly more frequently with CMV-related antigens than sera from age-, race-, and socioeconomic status-matched benign prostate hyperplasia groups. Specific reactivity against CMV-transformed cells of lymphocytes from prostatic cancer patients was also detected. These complex findings indicate that CMV may be involved in the development of prostatic neoplasia.