Monosodium glutamate (MSG) administration to neonatal mice results in destruction of the arcuate nucleus (AN) of the hypothalamus and numerous behavioral, endocrine and neurochemical sequelae. The present study assessed high-affinity neurotransmitter uptake into hypothalamic synaptosomes isolated from adult mice which were treated on postnatal day 4 with either MSG (4 mg/g) or saline. MSG treatment produced a significant reduction in synaptosomal uptake of dopamine (DA), choline (Ch) and GABA when expressed in terms of hypothalamic wet weight. However, MSG treatment resulted in a significant loss (70%) of synaptosomal protein and consequent increases in synaptosomal uptake of these neurochemicals when expressed per unit of synaptosomal protein. The results indicate that MSG treatment produced an overall reduction in net hypothalamic uptake, with surviving neuronal elements exhibiting an increased uptake which may reflect compensatory changes in these nerve terminals. MSG may thus disrupt pituitary and intrahypothalamic functions via its effects on neuronal systems of the AN.