Accessory signals, which include adhesion molecules, MHC-II molecules and cytokines, are necessary to foster the interaction between memory T cells and epidermal cells, that is required to promote cutaneous inflammatory responses. American cutaneous leishmaniasis (ACL) is characterized by a spectrum of immunological manifestations, and is a prototype disease for the study of regulatory mechanisms involved in immune protection against protozoal infection. In the present study, we show that diffuse cutaneous leishmaniasis (DCL) epidermis contains keratinocytes that do not express ICAM-I and HLA-DR molecules. Langerhans cells (LC) are within normal values or somewhat lower, and a very few cells expressing the HB15 molecule - a new described member of the Ig superfamily - are found in such lesions. Mucocutaneous leishmaniasis (MCL) epithelium shows an increased express ion of ICAM-I and HLADR molecules, few HBI5+ cells, and an absence of epithelial Le. Localized cutaneous leishmaniasis (LCL) epidermis displays ICAM-I + keratinocytes organized in patches, a uniform expression of HLA-DR, hyperplasia of LC, and numerous HB15+ cells. In all forms of the disease, infiltrating T cells express more LFA-1β than LFA-1α, but LFA-1β+ T cells are more abundant in LCL granulomas. In contrast, there are more LFA-1α+ T cells in DCL and MCL than in LCL granulomas. LCL lesions also show the highest numbers of HB15+ cells within the granuloma. These results indicate the importance of adhesion molecules in ACL lesions, and open new possibilities for therapeutic schemes oriented towards the control of cell migration.