Perturbation of the cutaneous water permeability barrier has been shown to result in many physiological events in keratinocytes, including upregulation of proinflammatory cytokine production. However, little is known about the effect of barrier disruption on Langerhans' cells (LC). In the present study, we examined whether acute barrier perturbation by acetone treatment or tape stripping affects the phenotypes and functions of LC in male hairless mice. Both procedures resulted in a two- to five-fold increase in the expression of MHC class II antigens, B7-2 and intercellular adhesion molecule-1 on LC, whereas no significant changes were detected in levels of B7-1. Levels of intracellular interleukin-1 beta, as determined by flowcytometry, were also increased 1 h after acetone treatment or tape stripping. LC obtained from barrier-disrupted mice induced a significant increase in syngeneic and allogeneic T-cell proliferation, compared to those from saline-treated mice. These results indicate that LC play a crucial role in maintaining cutaneous homeostasis against increasing exposure to external substances resulting from barrier disruption.