Abstract: During the past few years, it has become well established that the distal structural/functional domains of the neuron contain numerous mRNAs. However, there is a paucity of information on the composition and function of these unique mRNA populations. In this article, we review recent evidence to support the hypothesis that protein synthesis occurs in multiple subcellular compartments in the neuron, to include the axon and presynaptic nerve terminal. The studies we describe use the squid giant axon and photoreceptor neuron as model invertebrate motor and sensory systems, respectively. Initial cell-free translation studies and molecular hybridization analysis established that the giant axon contained a heterogeneous population of polyadenylated mRNAs. The application of differential mRNA display methodology greatly facilitated the isolation and identification of 29 of these mRNAs, which encode cytoskeletal proteins, molecular motors, translation factors, various nuclear-encoded mitochondrial mRNAs, and several novel mRNA species. RT-PCR analysis of RNA from squid brain synaptosomes confirmed the presence of these mRNAs in the presynaptic nerve terminal. The presence of these mRNAs in polysomes purified from the synaptosomal fraction establish that these messengers are actively translated in the terminal. Results of in vitro labeling studies demonstrate that a significant fraction of the nuclear-encoded mitochondrial protein derives from the local synthesis in the terminal. This finding calls attention to the intimacy of the relationship that has evolved between the nerve terminal and its energy-generating system. The role that local protein synthesis might play in the mammalian nervous system and in the neuronal response to stress is discussed.