The skin of albino mice given 5-aminolevulinic acid (ALA) by intraperitoneal injection rapidly developed the characteristic red fluorescence of protoporphyrin IX. Fluorescence microscopy of frozen tissue sections revealed intense red fluorescence within the sebaceous glands and a much weaker fluorescence within the epidermis and hair follicles. Little or no fluorescence was detected in the dermis, blood vessels, or cartilage of the ear. Light microscopy of skin taken at intervals after whole-body exposure of ALA-injected mice to photoactivating light revealed destruction of sebaceous cells, focal epidermal necrosis with a transient acute inflammation, and diffuse reactive changes in the keratinocytes. The dermis showed transient secondary edema and inflammation. The location and severity of the phototoxic damage correlated well with the location and intensity of the red fluorescence. The light-exposed skin appeared to recover completely except for a persistent reduction in the number of hair follicles.