vgf, a gene coding for a protein secreted through the regulated pathway, is rapidly up-modulated by nerve growth factor in PC12 cells and is expressed in vivo only in cell subpopulations of neuronal and endocrine origin. Here we demonstrate the following: (i) the nerve growth factor-dependent induction of vgf mRNA occurs at the transcriptional level and requires ongoing protein synthesis, (ii) lack of vgf expression in the nonneuronal cell line HTC is in part mediated by the presence of a repressor, (iii) a 110-base-pair sequence in the vgf promoter region contains positive and negative regulatory elements that partially account for its regulated expression, and (iv) a 47-base-pair oligonucleotide within this sequence specifically binds nuclear proteins that differ between vgf-expressing and non-expressing cells.