Hormone release from the pars intermedia is under inhibitory control of the hypothalamus. Control may be mediated via dopaminergic fibers which directly contact secretory cells. Administration of reserpine in vivo to adult male rats for four consecutive days results in major alternations in pars intermedia cytology. Cells show expanded areas and whorls of rough endoplasmic reticulum, as well as extensive Golgi zones with numerous dense granules. Some nerve fibers exhibit alterations in vesicle content, while others retain a more normal appearance. Freeze-fracture of glands from reserpine-treated animals provides evidence for exocytosis of granules, although such phenomena are not observed in thin sections. The ultrastructural findings suggest that reserpine alters the content of local inhibitory neurotransmitters in the pars intermedia, leading to unrestrained hormone release, followed by renewed granule synthesis.