The polyomaviruses comprise a class of small DNA tumor viruses within the papovavirus group of DNA viruses. Members of the polyomavirus class include polyomavirus of mice, simian virus 40 of monkeys, polyomavirus of hamsters, avian polyomavirus, and the JC, BK, and B-lymphotrophic viruses of humans. Of these viruses, the murine polyomavirus has been most thoroughly characterized with respect to the genetic elements and proteins involved in oncogenic transformation of mammalian cells. Oncogenic transformation of rodent cells by the murine polyomavirus requires the continued expression of the middle T antigen encoded by the virus. The middle T antigen is a membrane-associated phosphoprotein. All transformation-competent middle T antigens possess an associated tyrosine-specific protein kinase activity. One of the protein kinases associated with the middle T antigen is the product of the c-src gene. Two additional members of the src family of tyrosine protein kinases have also recently been shown to be associated with middle T antigen--the products of the c-yes and the fyn genes. These results indicate that the mechanisms through which polyomavirus transforms mammalian cells is by associating with and deregulating multiple cellular tyrosine protein kinases.