GAP-43 is a neuron-specific phosphoprotein that has been linked with the development and functional modulation of synaptic relationships. cDNAs for the human GAP-43 gene were used to reveal high overall levels of GAP-43 mRNA in a number of integrative areas of the neocortex, but low levels in cortical areas involved in the initial processing of sensory information, in several brainstem structures, and in caudate-putamen. Neurons expressing highest levels of GAP-43 mRNA were found by in situ hybridization to be concentrated in layer 2 of association cortex and in hippocampal pyramidal cells. Control studies showed that several other RNAs had regional distributions that were different from GAP-43, although the mRNA encoding the precursor of the Alzheimer amyloid beta protein followed a similar pattern of expression. These results suggest that a restricted subset of cortical and hippocampal neurons may be specialized for synaptic remodeling and might play a role in information storage in the human brain.