The developmental biology of mammalian cutaneous melanocytes spans the entire life cycle from embryo to senescent adult. This review focuses on the inelanocytes of the epidermis. Recent studies on neonatal mice indicate that melanoblasts of neural crest origin differentiate into epidermal melanocytes in response to signals provided by the local tissue environment, which may incorporate melanocyte-stimulating hormone and other hormones of pituitary origin in its action. In mice, there is a rapid disappearance of active epidermal melanocytes from the haired general body (trunk) skin during the 1st mo of life. Since active epidermal melanocytes persist in the relatively hairless skin of the appendages, some action of the local tissue environment is indicated here as well. An age-dependent decline in epiderrnal melanocytes occurs in humans over a period of many years. The fate of these melanocytes and the cause of their decline in humans and mice are not known. Several lines of evidence indicate that at least some melanocytes persist in an inactive form and may be stimulated to produce melanin on exposure to ultraviolet light. The local tissue environment influences not only the ability of epiderinal melanocytes to synthesize melanin but also the types of pigment-bearing bodies (melanosomes) that they manufacture. In recessive yellow mice, for example, pheomelanosome-like bodies are synthesized by epidermal melanocytes whereas those of the dermis produce eumelanosomes. The changes observed during the clinical course of human piebaldism and vitiligo indicate that studies on age-dependent modifications in normal mouse and human epidermal melanocytes are essential for an understanding of these and other pigmentary disorders.