The antigen-presenting cell function of the epidermis was investigated immunocytochemically in 16 dogs with different types of skin lesions induced by Leishmania infection. The degree of epidermal immunocompetence was evaluated according to the presence of Langerhans cells (LC) and keratinocytes expressing class II major histocompatibility complex (MHC II) molecules on the one hand, and the relative numbers of macrophages, T cells, and parasites in the dermis on the other, as described for human cutaneous leishmaniasis. In alopecic dermatitis, appropriate numbers of LC and MHC II- positive keratinocytes were shown to be associated with a mild T cell infiltration without significant numbers of parasites. By contrast, when the epidermis lacked antigen-presenting cells, as occurred in nodular lesions, macrophages and parasites massively infiltrated the dermis. Ulcerative lesions showed intermediate patterns of inflammation. These results suggest that dogs with alopecic dermatitis develop an effective control of the infection, whereas those with a generalized nodular disease mount an impaired immune response against the parasite. Skin lesions in dogs infected by Leishmania might not only have a prognostic value, but also represent a suitable model to study the natural course of human cutaneous leishmaniasis.