A screen designed to identify proteins that specifically bind to retinoic acid response elements resulted in the identification of a rat cDNA encoding a novel protein containing six Cys-Cys, His-Cys zinc fingers. This gene is expressed in a restricted fashion exhibiting distinct temporal and spatial patterns in the developing nervous system, primarily brain, spinal cord, sensory ganglia, retina, and nasal epithelia, as well as in the pituitary, and is referred to as neural zinc finger factor 1 (NZF-1). NZF-1 binds specifically to a cis-regulatory element of the beta-retinoic acid receptor (RAR beta) gene, as well as to other related DNA elements, including two in the upstream enhancer region of the mouse Pit-1 gene. In heterologous cells, NZF-1 activates transcription from promoters containing specific binding sequences and can synergize with other factors, such as Pit-1, to regulate gene expression. These results suggest that NZF-1 may exert regulatory roles in the developing and mature nervous system and in the pituitary gland. Identification of a second mouse gene highly homologous to NZF-1, encoded by a distinct genomic locus, reveals a dispersed gene family encoding proteins containing Cys-Cys, His-Cys motifs.