Fonsecaea pedrosoi is the major etiological agent of chromoblastomycosis, a chronic, suppurative, granulomatous mycosis usually confined to skin and subcutaneous tissues, presenting a worldwide distribution. The host defense mechanisms in chromoblastomycosis have not been extensively investigated. Langerhans cells (LC) are bone-marrow-derived, dendritic antigen-presenting cells of the epidermis, which constitutively express major histocompatibility complex (MHC) class II, and comprise 1-3% of total epidermal cells. LC are localized in suprabasal layers of the epidermis and in mucosa, where they play important roles in skin immune responses. The purpose of the present study was to evaluate the interaction of F. pedrosoi conidia or sclerotic cells with LC purified from BALB/c mice skin. We demonstrate here that LC phagocytose F. pedrosoi conidia but not sclerotic cells in the first 3 h of interaction, inhibiting hyphae formation during 12-hour coculture from both forms, internalized or not. Also, LC maturation, analyzed using CD40 and B7-2 expression, was inhibited by conidia, but not by sclerotic cells, indicating an important innate immunity function of LC against F. pedrosoi infection in these mice.