Abstract: External assault to the skin is followed by an epidermal response including synthesis of DNA, lipids, cytokines and migration of antigen presenting cells. MIP‐3α (CCL20, LARC, Exodus‐1, Scya20) is a recently described C‐C chemokine, predominantly expressed in extralymphoid tissue, which is known to direct migration of dendritic cell precursors and memory lymphocytes to sites of antigen invasion. We assessed the expression of MIP‐3α in human skin using semi‐quantitative polymerase chain reaction. In vivo, MIP‐3α mRNA was constitutively expressed at low levels in untreated human epidermis. After acute disruption of the epidermal permeabiltiy barrier MIP‐3α mRNA was upregulated in the epidermal fraction, whereas dermal MIP‐3α mRNA levels remained unchanged. In vitro, MIP‐3α was increased in cultured keratinocytes treated with IL‐1α and TNF‐α and was present in immature and mature dendritic cells, THP‐1 monocytic cells and activated T cells. Finally, skin biopsies from patients with psoriasis, contact dermatitis and mycosis fungoides showed abundant expression. In biopsies from atopic dermatitis and graft vs. host disease a weak signal was present, whereas no expression was found in scleroderma and toxic epidermal necrolysis. We conclude that regulation of MIP‐3α mRNA is part of the epidermal response to external assault. Its upregulation may represent a danger signal for increased immunosurveillance in barrier disrupted skin and inflammatory skin conditions with impaired barrier function to counteract potential antigen invasion.