Previously, we have showed that artificial epidermal permeability barrier disruption leads to an increase in epidermal Langerhans' cell (LC) density within 24 h. We now asked if this is accompanied by an enhancement of allergic contact dermatitis. Barrier disruption was induced by acetone on the upper arms in 6 volunteers with known sensitization to nickel, fragrance mix, or p-phenylenediamine. Twenty-four hours after this treatment the relevant allergen was applied without occlusion or with Finn chambers. Twenty-four hours after application of the allergen, clinical grading and transepidermal water loss (TEWL) measurements were performed and biopsies were taken. Immunohistochemical stainings for LCs (anti-CD1a, Leu6) and for epidermal proliferation (Ki-S3) were performed. Open applications of the allergens after acetone pretreatment resulted in strong allergic test reactions. TEWL, which showed a 70% recovery 24 h after acetone treatment, was increased again 4-fold by the allergic test reactions. LC density, which was increased by 80% 24 h after acetone-induced barrier disruption, was further enhanced 2.4-fold in total. Epidermal proliferation showed a 6-fold increase after open application of the allergens. Under patch test conditions after acetone pretreatment very strong bullous reactions were observed. We conclude that the increase in epidermal LC density induced by epidermal permeability barrier disruption is accompanied by an enhanced response in allergic contact dermatitis.