We have examined the effects of adrenalectomy (ADX) on neuropeptide Y (NPY) content in the posterior pituitary of the rat. In rats given 2% saline to drink for 12 days, plasma osmolality increased to 343 ± 18 compared to 291 ± 5 mosm/kg in control animals on water (mean ± SEM). Hypertonic saline treatment resulted in increased posterior pituitary NPY content measured by radioimmunoassay (2.42 ± 0.36 ng) compared to the control group (1.18 ± 0.16 ng). Total NPY immunoreactivity in tissue extracts coeluted with synthetic NPY(l-36) on reversed-phase high-performance liquid chromatography. In ADX rats given 2% saline to drink, plasma osmolality increased to 355 ± 35 mosm/kg, but posterior pituitary NPY content was not different from the control group (1.41 ± 0.11 ng). Immunohistochemical staining for NPY in the posterior pituitary also revealed a saline-induced increase in the number of NPY-immunoreactive nerve fibers, an increase which was not evident in the ADX group. No NPY immunoreactivity was observed in the intermediate zone. These results are the first evidence that the saline-induced increase in NPY in the posterior pituitary is under corticosteroid control.