Psoriasis is a chronic inflammatory and proliferative epidermal skin disease associated with prominent new vessels in the dermis. Heretofore, unresolved was the question which skin element causes stimulation of vessel formation in this lesion: the epidermis, the dermis, vessels themselves, inflammatory cells, and so forth. It has been argued that the dermis by means of its vessels is responsible for the rapid and prominent epidermal growth and that psoriasis is simply a dermal-induced epidermal disease. Recognizing that vascular proliferations do not occur in the absence of an angiogenic stimulus we asked where in psoriatic skin is that angiogenic element found. By using the rabbit cornea angiogenic assay, the vessel-stimulating properties of epidermis and dermis (separated after cold trypsinization overnight), collected from psoriatic-plaque skin and normal skin both nonpsoriatic and psoriatic patients, were measured. The corneas were examined on days 2, 4, 8, 10, and 12 and graded from 1 to 5+ for vessel growth. Psoriatic plaque epidermis revealed a 4 to 5+ stimulus (8 of 12 corneas). Epidermis from normal subjects or from nonlesional psoriatic patient skin also revealed a 4 to 5+ stimulus (3 of 5 and 5 of 8, respectively). In no case was the dermal implant from normal (7 implants) or psoriatic patients (3 implants of lesional skin) angiogenic. The angiogenic activity of epidermis is stable to freezing and boiling. This study indicates that the vessel-stimulating properties of psoriatic and nonpsoriatic skin are associated with the epidermis and that the developing psoriatic lesion may involve complex epidermal to dermal as well as dermal to epidermal signals.