Lysosomes, as demonstrated biochemically in the liver, are subcellular particles containing a group of hydrolytic enzymes enclosed by a membrane-like barrier. They are apparently inactive in the normal state, but when subjected to various forms of injurious treatments the enzymes associated with them are released. The existence of lysosomes in skin is demonstrated in the present communication. The resistance of this tissue to homogenization makes the biochemical study of lysosomes very difficult. Yet, by the application of histochemical methods to sections of skin, it has been possible to use the same criteria as would be employed in the biochemical characterization of these organelles. By using the controlled-temperature freezing-sectioning method it has been possible to obtain frozen sections in which cytoplasmic particles could be demonstrated which were enzymically inactive for acid phosphatase until the sections were subjected to such injurious treatments as heat, repeated freezing and thawing, hypotonic solutions, distilled water, and ‘triton-X-100’. Since the subcellular particles demonstrated behaved in the same manner as lysosomes prepared biochemically from liver, it is concluded that the cytoplasmic organelles staining for acid phosphatase in mouse skin are lysosomes as biochemically defined.