While clinical observations suggest that trauma to the skin plays a critical role in the induction of skin lesions in some skin diseases, the mechanism by which these lesions are induced is not known. We have postulated that minor trauma to the skin may lead to the expression of critical adhesion molecules on epidermal endothelial cells (E-selectin) and pro-inflammatory cytokines, which would predispose these areas to the development of skin lesions. In order to test this hypothesis normal inner arm skin of 11 normal subjects was gently rubbed with a pencil eraser for 2 min. Four hours after rubbing, skin biopsies were obtained from the rubbed site and from adjacent normal, unrubbed inner arm skin. Expression of E-selectin, intercellular adhesion molecules (ICAM-1) and the mRNA of selected cytokines was studied utilizing real time polymerase chain reactions. Biopsies were also examined for the presence of an inflammatory infiltrate and for the presence of E-selectin and ICAM-1. No clinical or histologic changes were seen in the skin expression/unrubbed skin expression = 9.0; (median ratio rubbed skin expression/unrubbed skin expression range 0.9-161.0), ICAM-1 (median rubbed skin expression/unrubbed skin expression = 3.2; range 0.9-19.8), IL-8 (median rubbed skin expression/unrubbed skin expression = 6.6; range 2.6-57.3) and IL-10 (median rubbed skin expression/unrubbed skin expression = 13.1; range 2.4-29.0) was noted. Immunohistochemistry revealed the presence of E-selectin in the dermal blood vessels in three of four subjects 4 h after rubbing but not in the unrubbed skin. Changes in ICAM -1 or HLA-DR deposits were seen in the rubbed compared with the unrubbed skin. These findings demonstrated that minor trauma to skin may induce expression of E-selectin, ICAM-1 and IL-8, which may make the skin a more permissive site for the development of inflammatory reactions. These findings may play an important role in the development of skin lesions in areas of minor trauma.