The goal of the present study was to determine whether a correlation between the clinical stage of cutaneous leishmaniasis lesions and in vitro parameters of cell-mediated immunity could be established. For this purpose, we measured lymphocyte proliferation, using a total lymphocyte proliferation (TLP) blood assay, and leishmanicidal effector activity using peripheral blood mononuclear cells (PBMC) in a three-day assay. The parameters of leishmanicidal activity measured included percent infected monocytes and number of amastigotes per 100 infected monocytes 24 and 72 hr after infection. Three groups of people were studied: a group of patients in the course of the disease, a group of immune individuals, and unexposed controls. The results of the study suggested that the ability of PBMC to kill parasites increased in patients as the lesions cured, and was highest in immune individuals. In contrast, the TLP response once positive, did not increase after cure. In approximately 30% of the patients who were retested on several occasions during the course of the disease, a positive response reversed to negative both in the TLP and the effector assays while the lesions were still active. In approximately 50% of these cases, the response eventually became positive again. The data presented show that effector activity and prolifeation correlate with immunity, and suggest that marked heterogeneity characterizes the immune response in the course of active disease.