The octamer binding transcription/DNA replication factor Oct-1 is present in virtually all cell types including proliferating cell lines of neuronal origin but is not detectable in mature non-dividing neurons. Cell cycle arrest in G0/G1 and morphological differentiation of a neuronal cell line is accompanied by a decline in the level of Oct-1 DNA binding, although the level of DNA binding by another octamer binding protein, Oct-2 is unaltered. This effect is paralled by a decline in the level of the Oct-1 mRNA in the non-dividing cells. The decrease in Oct-1 levels occurs only with the production of a mature, non-dividing neuronal phenotype and not when the cells are arrested in late G1 and do not undergo morphological differentiation. The potential role of Oct-1 and other octamer binding proteins in gene regulation in neuronal cells and in their differentiation is discussed.