Regulation of transcription in eukaryotes is mediated by the specific interaction between cellular factors and promoter sequences. Cis-acting DNA sequences, frequently located upstream of the TATA box, have been implicated in modulating the expression of many genes. We are interested in the transcriptional regulation of proto-oncogenes because they may have a pivotal function in cell growth and differentiation. Expression of the proto-oncogene c-fos is induced in response to a variety of growth factors and differentiation-specific agents. The viral cognate of the c-fos gene is the resident transforming gene of FBJ-murine osteosarcoma virus which causes bone tumours in vivo and cellular transformation in vitro. We report here that transcription of the human c-fos gene is modulated by negatively and positively acting cellular factors.