Infection of a wide variety of rodent and human cells with simian virus 40 (SV40) will result in the full phenotypic transformation of these cells and subsequent injection of such transformed cells into syngeneic hosts demonstrates that they are highly tumorigenic. The virus itself is relatively harmless to whole animals as only newborn hamsters appear to be susceptible to tumor formation. Early studies with the virus showed that the early region of the genome which encodes two tumor antigens, large T and small t, was responsible for this activity and that the large T antigen was necessary for transformation (see Refs. 1-3 for reviews). Indeed, vectors which express only the large T antigen of SV40 have shown oncogenic potential demonstrating that the large T antigen is both necessary and sufficient for the ability of the virus to transform both established and primary cells [4-9]. Small t antigen does not have transforming activity of its own but is capable of enhancing the activity of limiting levels of large T antigen ([10, 11] and refer-ences therein). We will focus on large T antigen in this review.