Our current project is to test the hypothesis that a dysfunction of the cyclic AMP regulatory system in the epidermis constitutes the major biochemical abnormality in psoriasis. On the basis of this hypothesis, it was postulated that a low cyclic AMP level accounts for the high mitotic rate and glycogen accumulation observed in this disease. In 10 cases of established psoriasis, we measured cyclic AMP levels in micro-dissected (frozen-dried) epidermis from the psoriatic and healthy skin of the same patient. The level was slightly higher in psoriatic epidermis than in uninvolved epidermis; thus the above hypothesis was not proved. In another model in which pig epidermis was irradiated by UV lights (our preliminary experiments), high cyclic AMP level also coincided with high mitotic rates and marked glycogen accumulation. When epidermal slices were tested for hormonal activation of cyclic AMP levels in epidermis, epinephrine increased the level about 20 times more in the uninvolved than in the psoriatic skin. Since cyclic AMP-phosphodiesterase appears normal in both psoriatic and uninvolved epidermis (their high and low Kms were about the same), a major biochemical lesion is present in psoriatic lesions in regard to their inability to respond to epinephrine stimulation. How the low adenylate cyclase stimulation accompanies a high cyclic AMP level in psoriasis needs to be studied further. BIBLIOGRAPHIC REFERENCES: K. Yoshikawa, K. Adachi, V. Levine and K.M. Halprin: Micro-determination of cyclic AMP levels in human epidermis, dermis and hair follicles. Brit. J. Derm. 92: 241-248, 1975; K. Yoshikawa, K. Adachi, K.M. Halprin and V. Levine: Cyclic AMP in skin: effects of acute ischaemia. Brit. J. Derm. 92: 249-254, 1975.