The cytoarchitecture of the adult central nervous system is expressed by proteins specific to individual cell types. In this investigation, a subclass of these proteins, the neuron-specific phosphoproteins, was examined after the administration of trimethyltin (TMT), a neurotoxicant which preferentially damages neurons in limbic structures. After acute administration of TMT, effects on neuronal phosphoproteins were examined by three separate techniques: (1) endogenous phosphorylation of total synaptic membrane proteins; (2) radiometric assay of synapsin I, a neuron-specific phosphoprotein associated with synaptic vesicles; and (3) radioimmunoassay of synapsin I and protein III, another synapsin specific, synaptic vesicle-localized phosphoprotein. The authors findings are consistent with the neuropathological effects of this compound and suggest that neuron-specific phosphoproteins may be useful biochemical indicators of neurotoxicity.