The pars intermedia was investigated by electron microscopy, with relation to changes in skin color, in frogs ( Rana nigromaculata) that were first adapted to a white background, then subjected to extirpantion of the median eminence, and subsequently kept on the white background for various periods. It was found that: 1. Following extirpation, the animals begin to darken on a white background and to lose their background adaptability. After 2–3 h, the extirpated animals become intensely dark and remain so for at least 2 weeks. From 3 or 4 weeks on, such animals begin to adapt to their background again and slowly blanch, although they do not lighten at 6 months as fully as do intact animals at the end of that period. 2. The pars intermedia cells at the irreversible, dark stage of the extirpated animals show a progressive decrease in the number of secretory granules in the cytoplasm, followed by an incease in the amount of rough-surfaced endoplasmic reticulum. In the 2-day animals, there is a marked diminution of the secretory granules and a slight expansion of the rough-surfaced endoplasmic cisternae. At this stage, degenerative changes appear in the ordinary nerve endings that make synaptic contact with the pars intermedia cells. 3. The pars intermedia cells at the adaptive, light stage of the extirpated animals indicate the successive accumulation of secretory granules in the cytoplasm, followed by the reduction of rough-surfaced endoplasmic reticulum. The appearance of the cells of the 6-month animals seems very similar to that seen in the preoperative, white-background-adapted animal. At this stage, the degenerated synapses rapidly progress toward normal. These findings were discussed with particular respect to the hypothalamic neural inhibition of the pars intermedia, leading to the conclusion that this inhibition appears to operate first on the release mechanism of melanophore-stimulating hormone (MSH) in the gland through the ordinary, possibly adrenergic, nerve fibers originating in the hypothalamus. Furthermore, it was suggested that the synthesis of MSH is regulated by a feedback mechanism activated by the hormone stored in the gland.