Expression of the middle-T antigen of polyomavirus is sufficient to induce transformation of fibroblasts in culture and tumour formation in whole animals. Middle-T can form a complex with the cellular src gene product (p60c-src) and can be phosphorylated by p60c-src in vitro. Studies using middle-T mutants have suggested that the association of middle-T with p60c-src may be necessary but not sufficient for transformation. Therefore, we addressed the possibility that middle-T could interact with other tyrosine protein kinases structurally related to p60c-src. Using antibody raised against a fusion protein between beta-galactosidase and amino-terminal sequences of p90gag-yes from Y73 virus (anti-yes antibody), we have found that middle-T can associate with and be phosphorylated by the c-yes proto-oncogene product, a protein of relative molecular mass (Mr) 62,000 (62K). This raises the possibility that the middle-T-p62c-yes complex contributes to transformation by polyomavirus.