Hamster polyomavirus (HaPV) is associated with lymphoid and hair follicle tumors in Syrian hamsters. The early region of HaPV has the potential to encode three polypeptides (which are related to the mouse polyomavirus early proteins) and can transform fibroblasts in vitro. We identified the HaPV middle T antigen (HamT) as a 45-kDa protein. Like its murine counterpart, HamT was associated with serine/threonine phosphatase, phosphatidylinositol-3 kinase, and protein tyrosine kinase activities. However, whereas mouse middle T antigen associates predominantly with pp60csrc and pp62c-Yes, HamT was associated with a different tyrosine kinase, p59fY". The ability of HaPV to cause lymphoid tumors may therefore reside in its ability to associate with p59fyf, a potentially important tyrosine kinase in lymphocytes. Hamster polyomavirus (HaPV) was first described in association with spontaneously arising skin tumors in a colony of Syrian hamsters in Germany, with as many as 10% of hamsters showing overt multiple hair follicle tumors by the age of 3 months (25, 27). However, inoculation of the virus into newborn hamsters from a separate virus-free colony led predominantly to induction of lymphoma an.