T HE majority of histochemical investigations of skin have been conducted in the past ten years. The most complete review is a text by Montagna,’ but much important work has been published since this excellent review. In this paper discussion of the histochemistry of skin will be restricted to those techniques which attempt to show specific chemical entities in skin with specific methods which appear rational and are for the most part acceptable as specific chemical methods for identification. This, of course, eliminates all the literature dealing with such nonspecific staining methods as hematoxylin and eosin, orcein, Gomori trichrome, van Gieson, pH-sensitive dyes, etc. There are still substantial limitations on the chemicals which can be specifically identified in skin by histochemical staining techniques. Among the agents which can be identified in skin are polysaccharides, fats, sulfhydryl and disulfide groups of proteins, free amino groups of proteins and lipoproteins, calcium, iron, ribonucleic acid, desoxyribonucleic acid, and a large group of oxidative and hydrolytic enzymes. The identification of enzymes by histochemical techniques is becoming one of the largest segments of the science of histochemistry. The main advantage of histochemical techniques over strictly biochemical methods is that one is able to localize directly in the cell where the chemical in question resides. An example of the advantage of histochemical technique is the identification directly of the melanocyte as the cell in the epidermis which contains tyrosinase.2 By exposing prepared human skin to tyrosine one can show that melanin is formed in the melanocytes and not in other cells of the epidermis. It is also possible with autoradiographs to show that melanocytes alone contain tyrosinase.3 It must be realized that conventional biochemical techniques are desirable whenever strict localization is not part of the problem. The histochemist and his subject are hybrids of the genes of chemistry and anatomy. A deficiency in either results in a gross distortion of the product. Original work in histochemistry was published by Unna,4 a prolific dermatologist who contributed a great deal to the origin of this field. Lison5 was an important later contributor. The field has been developed mostly in the past 15 years, with such contributors as Gomori,6 Pearse,’ Seligman and Lillie,* and others forming a nucleus for this growing branch of study.