The oncoprotein of the Simian virus 40, SV40 large T-antigen (Tag), is reported to target and inactivate growth-suppressive proteins such as the retinoblastoma (Rb) family and p53 leading to transformation of human cell lines in vitro, to produce tumours in rodents, and to be detected in several human cancers including mesothelioma. In support of the potential role of SV40 Tag in the pathogenesis of certain human cancers, we have found SV40-like sequences in 8/25 bioptic specimens of mesothelioma from patients with exposure to asbestos fibres. We have also demonstrated that the SV40 Tag detected in human mesothelioma binds the retinoblastoma family protein pRb2/p130 in 5/5 specimens studied. We submit that the tumorigenic potential of SV40 Tag in some human mesotheliomas may arise from its ability to interact with and thereby inactivate several tumour and/or growth suppressive proteins in cooperation with asbestos fibres in inducing pleural mesothelioma.