Human and murine skin are prominent extrapituitary sources and targets for POMC products. The expression of, for example, ACTH, alpha-MSH, beta-endorphin, and MC-1-receptors fluctuates during synchronized hair follicle cycling in C57BL/6 mice. Since hair growth can be induced by ACTH injections in mice and mink, and since high doses of MSH peptides modulate epidermal and/or follicle keratinocyte proliferation in murine skin organ culture, some POMC products may operate as locally generated growth modulators, in addition to their roles in cutaneous pigment and immunobiology. Intrafollicularly generated ACTH and alpha-MSH as well as their cognate receptors may assist in the maintenance of the peculiar immune privilege of the anagen hair bulb. Possibly, they are also involved in the development of the follicle pigmentary unit, with whose generation their expression coincides. Given that murine skin also expresses (in a hair-cycle-dependent way) CRH and CRH-R, which control pituitary POMC expression and in view of the fact that CRH arrests follicles in telogen, this suggests the existence of a local skin POMC system (SPS). This may be an integral component of cutaneous stress response-systems, and may most instructively be studied using the murine hair cycle as a model.