Multiple signaling pathways are thought to control the selective expression of genes over the course of neuronal differentiation. One approach to elucidating these pathways is to identify specific cis-acting elements that serve as the final targets for these signaling pathways in neural-specific genes. We now identify a novel repressive element from the growth-associated protein 43 (GAP-43) gene that can contribute to neuron-specific gene expression by inhibiting transcription in a wide range of non-neuronal cell types. This repressive element is located downstream of the GAP-43 TATA box and is highly position-dependent. When transferred to viral promoters this element preferentially inhibits transcription in non-neuronal cells. Electrophoretic mobility shift assays show that the repressive element comprises at least two protein recognition sites. One of these is a novel sequence motif that we designate the SNOG element, because it occurs downstream of the TATA boxes of the synaptosomal-associated protein of 25 kDa and neuronal nitric oxide synthase genes, as well as the GAP-43 gene. The GAP-43 repressive element is distinct in sequence and position dependence from the repressor element 1/neuron-restrictive silencer element previously described in other neural genes and therefore is a likely target for a distinct set of signaling pathways involved in the control of neuronal differentiation.