Background: A large number of skin diseases, including atopic dermatitis and psoriasis, appear to be precipitated or exacerbated by psychological stress. Nevertheless, the specific pathogenic role of psychological stress remains unknown. In 3 different murine models of psychological stress, it was recently shown that psychological stress negatively impacts cutaneous permeability barrier function and that coadministration of tranquilizers blocks this stressinduced deterioration in barrier function. Objectives and Methods: The relationship between psychological stress and epidermal permeability barrier function was investigated in 27 medical, dental, and pharmacy students without coexistent skin disease. Their psychological state was assessed with 2 well-validated measures: the Perceived Stress Scale and the Profile of Mood States. Barrier function was assessed simultaneously with the stress measures at periods of presumed higher stress (during final examinations) and at 2 assumed, lower stress occasions (after return from winter vacation [approximately 4 weeks before final examinations] and during spring vacation [approximately 4 weeks after final examinations]). Results: The subjects as a group demonstrated a decline in permeability barrier recovery kinetics after barrier disruption by cellophane tape stripping, in parallel with an increase in perceived psychological stress during the higher vs the initial lower stress occasions. During the follow-up, presumed lower stress period, the subjects again displayed lower perceived psychological stress scores and improved permeability barrier recovery kinetics, comparable to those during the initial lower stress period. Moreover, the greatest deterioration in barrier function occurred in those subjects who demonstrated the largest increases in perceived psychological stress. Conclusion: These studies provide the first link between psychological status and cutaneous function in humans and suggest a new pathophysiological paradigm, ie, stress-induced derangements in epidermal function as precipitators of inflammatory dermatoses.