INTRODUCTION: The Montenegro skin test reaction and leishmaniasis lesions share fundamental characteristics of a delayed type hypersensitivity reaction. OBJECTIVES: To determine whether the Montenegro skin test reaction (response to leishmanin) might approximate and thereby provide insight into the early inflammatory and immune response to Leishmania infection. MATERIALS AND METHODS: We compared the inflammatory response in biopsies of acute (evolution time < or = one month), and chronic lesions (evolution time > or = 6 months) with the Montenegro skin test reaction in the corresponding patients, and with the Montenegro skin test of asymptomatically infected volunteers. RESULTS: The proportion of CD4+ and CD8+ T lymphocytes, mononuclear phagocytes and granulocytes were similar in acute lesions and in their corresponding Montenegro skin test reactions. In contrast, CD4+ lymphocytes (32.6%) represented a significantly lower, and B cells (20%) and macrophages (27%) a significantly higher proportion of the cellular infiltrate in chronic lesions as compared to reactions in the corresponding skin test site (CD4+: 43.7%, B cells: 0.9%; macrophages: 17.5%). CD8+ T lymphocytes and macrophages were positively associated (P = 0.038) in the Montenegro skin test of asymptomatically infected individuals whereas CD8+ and CD4+ T cells were positively associated in the Montenegro skin test of chronic patients (P = 0.002). Notably, B cells were markedly more frequent in chronic lesions (20%) than in acute lesions (5.3%) (P = 0.002). CONCLUSION: The Montenegro skin test distinguished the cellular immune response to Leishmania in asymptomatic infection and chronic disease and may provide a surrogate of the early response to infection.