The peripheral changes in the uninvolved skin adjacent to the extending psoriatic lesions may represent early events. The sequence of these events remains controversial. In the present study we evaluated epidermal and dermal aspects of the margin of the progressive psoriatic plaque, the distant uninvolved skin and normal healthy skin, using immunohistochemistry with markers for keratinization, proliferation and connective tissue: filaggrin, involucrin, Ki-67 and tenascin. The results showed that: (i) processes in distant uninvolved skin were comparable with the observations in normal skin; (ii) in the margin zone of the spreading psoriatic lesion, following the increased appearance of tenascin, the transition into parakeratosis, abnormal expression of filaggrin, involucrin and recruitment of cycling epidermal cells, happened simultaneously. The simultaneous normalization of these epidermal processes might be a consequence of a signal which is simultaneously transduced to the basal and suprabasal cell layers of the epidermis. Based on the present results and earlier findings, we would like to propose a triple stage model for the development of the psoriatic lesion: Stage 1, involvement of the stroma; stage II, inflammatory infiltrate formation and penetration into the upper layers of the epidermis, with suprabasal expression of keratin 16; stage III, recruitment of cycling epidermal cells and abnormal terminal differentiation. Further studies are required on the regulation of tenascin expression, focusing on factors derived from the stroma affecting both recruitment of cycling epidermal cells, involucrin and filaggrin expression. An intermediate step in the dermo-epithelial interrelation is the inflammatory infiltrate, penetrating into the most superficial zone of the epidermis, and the suprabasal expression of keratin 16.