We have examined whether psoriasis is associated with systemic effects on epidermal Langerhans cell (LC) function and, specifically, the migration of LCs from the skin. Compared with normal skin, the frequency and morphology of epidermal LCs in uninvolved skin from patients with psoriasis was normal. However, mobilization of these cells in response to stimuli that normally induce migration (chemical allergen, tumor necrosis factor alpha [TNF-alpha], and interleukin-1beta [IL-1beta]) was largely absent, despite the fact that treatment with TNF-alpha and IL-1beta was associated with comparable inflammatory reactions in patients and controls. The failure of LC migration from uninvolved skin was not attributable to altered expression of receptors for IL-1beta or TNF-alpha that are required for mobilization, nor was there an association with induced cutaneous cytokine expression. Although a role for altered dynamics of LC migration/turnover has not been formally excluded, these data reveal a very consistent decrement of LC function in psoriasis that may play a decisive role in disease pathogenesis.