Elements controlling tissue-specific expression of the rat albumin gene reside within roughly 150 bp upstream of the transcriptional initiation site. We show here by DNAase I footprinting assays that at least four distinct factors present in extracts derived from cells expressing albumin interact with these sequences. One of these factors is closely related or identical to nuclear factor 1 (NF1). Extracts from nonhepatic tissues or from dedifferentiated hepatoma cells that do not transcribe the albumin gene display a different pattern of DNA-protein interactions. Mixing experiments show that the variant pattern of dedifferentiated cells is dominant over that of differentiated ones, suggesting that nonexpressing cells contain dominant negatively acting factors.