Although stress is thought to worsen inflammation diseases, the mechanism is not known. Therefore, long period of isolation was administered to BALB / c male mouse as chronic mental stress, and the influence on contact dermatitis (CS) and function of Langerhans cells (LC) and keratinocytes (KC) were analyzed. As a result, by chronic stress the CS responses and the antigen presenting ability of LC were markedly enhanced, while the antigen presenting ability, IL-1-α and TNF-α (inflammatory cytokine) production and proliferative activity of KC were drastically reduced. Then, RNA of KC from mice received isolation stress was extracted and mRNA expression for various genes was analyzed using RT-PCR method. As preliminary experiments mRNA expression by KC after stimulation with phenol, a primary irritant, and trinitrochlorobenzene (TNCB), a contact sensitizer, were analyzed. As a result, only adhesion molecule ICAM-1 mRNA expression was induced by the former, while marked expression of mRNA for ICAM-1, E-cadherin (adhesion molecule), transglutaminase (differentiation marker), c-fos and c-myc (immediate early genes), corticotrophin releasing hormone receptor and substance P receptor ( neurotransmitter related), and IL-1-α and TNF-α were observed by the latter. Chronic stress up-regulated these mRNA transiently. However, application of TNCB to chronically stressed mouse, only expression of mRNA for transglutaminase and substance P receptor by KC was increase, and mRNA expression for other genre was reduced compared to control. These results suggested that by chronic stress the function of LC is enhanced, while function and differentiation of KC are impaired and that substance P released from neurofibers is related to these modulations.