The c‐fos proto‐oncogene is rapidly and transiently induced by a variety of extracellular stimuli. We have previously shown that conditioned media from v‐sis transformed NRK cells rapidly induces a DNA binding protein which binds to a conserved sequence upstream of the human c‐fos gene. We now show that purified recombinant c‐sis/PDGF can induce this binding activity which we have termed SIF, for sis‐inducible factor. Oligonucleotides which bind to the SIF protein will confer sis/PDGF inducibility onto a truncated, unresponsive c‐fos promoter. However, sequences lying between ‐100 and ‐57 of the c‐fos gene are required for this induction. The sis‐responsive element functions independently of a region of dyad symmetry previously identified as the serum responsive element (SRE). The time course of c‐fos expression driven by the sis‐responsive element is similar to that mediated by the SRE. Unlike the SRE, which can respond to signals generated by sis/PDGF, serum or phorbol esters, the SIF binding element mediates c‐fos induction only in response to sis/PDGF. The SRE and SIF elements function in an additive manner to stimulate the transcription of the c‐fos gene in response to sis/PDGF.