Abstract Adult rats treated neonatally with monosodium glutamate (MSG) exhibit lesions in the arcuate nucleus of the hypothalamus. Following MSG lesioning, dopamine content in median eminence/arcuate nucleus (ME/AN) tissue extracts declined by 60–70%. Substance P (SP) content as determined by radioimmunoassay was significantly decreased in the paraventricular nucleus (PVN) (531 ± 30 pg, mean ± SEM) compared to controls (871 ± 110 pg) but was unchanged in ME/AN extracts. Substance K (SK) content decreased to 257 ± 20 pg in the PVN of lesioned animals compared to controls (367 ± 31 pg) and the ME/AN content of SK was also significantly decreased (236 ± 36 pg compared to control levels of 619 ± 65 pg). The CRF-41 content of the PVN and ME/AN was unchanged by MSG lesioning, indicating that these areas are not affected by MSG. The partial depletion of SP and SK in the PVN following MSG treatment provides evidence that at least some of the neurokinin content of the PVN may originate in cell bodies of the arcuate nucleus. However, the lack of response of ME/AN SP to MSG treatment may suggest that the arcuate nucleus is not the major source of SP in the median eminence.