Nerve growth factor (NGF) is required for the development and survival of sympathetic and neural crest-derived sensory neurons. The mechanism of action of NGF has been extensively studied in the NGF responsive rat pheochromocytoma cell line, PC12. When treated with NGF, PC12 cells initiate neurite outgrowth and differentiate into cells with a neuronal phenotype. This process is prevented by RNA synthesis inhibitors. NGFI-B is a gene, identified by differential hybridization, that is rapidly, but transiently induced in PC12 cells by NGF The nucleotide sequence of the NGFI-B gene was determined, and it encodes a 61 kd protein with strong homologies to members of the glucocorticoid receptor gene family. The two regions of homology between NGFI-B and this family of ligand-dependent transcriptional activators are the region corresponding to the DNA-binding domain and the region comprising the ligand-binding domain near the COOH-terminus. NGFI-B, as a possible ligand-dependent transcriptional activator induced by NGF, may play a role in initiating NGFinduced differentiation.