Polyoma virus induced tumorigenesis is controlled by T-cells, while B-cells clear virus infection. In order to study if T-cells can override the tumorigenic effect of a long term disseminated viral infection, the tumorigenicity and persistence of polyoma virus in antibody deficient adult and newborn infected X-linked immunodeficient (XID) and microMT mice was followed. In newborn infected XID and CBA control mice (sensitive to tumorigenesis), the frequency of tumor development was similar, and viral DNA was persistent at least 10 months p.i. In polyoma-infected newborn and adult microMT, and control C57BL/6 mice (resistant to tumorigenesis) as well as in adult XID and CBA control mice, no polyoma tumors were observed. Nevertheless, viral DNA was detected in most tissues in all microMT mice throughout the 5-7 month observation period, whereas in the remaining groups of mice persistent viral infection was limited or not detected. We suggest that the tumorigenic potential of an extensive persistent polyoma virus infection can be overcome as long as a functional T-cell system is present.