Growth-associated protein-43 (GAP-43) is a developmentally regulated, fast-axonally transported phosphoprotein whose synthesis and transport are enhanced during periods of growth and synaptic terminal formation. GAP-43 is a substrate of protein kinase C and is identical to protein F1, a phosphoprotein which is regulated during long-term potentiation in the hippocampus. In order to characterize the cellular localization of GAP-43, we have raised a specific antiserum against it, and used this as a probe to show that GAP-43 is neuron-specific, and is localized to growing neuronal processes in developing rat brain, and to presynaptic terminals in both the peripheral and central nervous system. In the mature CNS, GAP-43 immunoreactivity is present in most neuropil areas, but is especially dense in the molecular layers of the cerebellum, neocortex, and the hippocampus, structures known to exhibit synaptic plasticity. Its localization, together with biochemical data concerning the dynamics of its synthesis and its identity as protein F1, suggest that GAP-43 may be involved in axon growth in the developing nervous system, and in some aspect of synaptic plasticity in the mature CNS. These data also suggest that axon growth and synaptic plasticity in the brain may be regulated by a common mechanism, both involving the protein kinase C-mediated phosphorylation of GAP-43.