We found local sequence-similarity between the non-catalytic region of the Rous sarcoma virus oncogene product, p60v-src, and the core region of cytoskeletal keratin through an extensive similarity search of segments of proteins. The segments showing similarity in p60v-src were in the region that is important for morphological transformation, and corresponded to segments with unique structural features predicted for intermediate filament proteins. We suggest that cellular components related with intermediate filament proteins or the sequence shared by the two proteins may be involved in the regulation of the kinase activity or substrate specificity of p60v-src.