It has been found that 334 bases of the 5' flanking region of the human retinol-binding protein (RBP) gene contain sufficient information to direct accurate and specific transcription in human hepatoma but not in HeLa cells. Dissection of this region reveals the existence of at least three distinct controlling elements: an enhancer, which can activate promoters in a variety of cell lines and is therefore non-tissue specific; a negative cis-acting element, which apparently binds a repressor molecule not present or non-functional in hepatoma cell lines; a promoter element. Transcription is confined to hepatoma cells only when both the negative element and the promoter element are present.