Leishmaniasis is an important parasitic disease affecting millions worldwide. In attempts to understand the clinical relevance of immunological measurements as determined using flow cytometry, several immunological phenotypes were determined for a group of well defined human leishmaniasis patients and correlated with clinical measurements of the disease (Montenegro skin test (MST) and lesion area). The analysis demonstrated a positive correlation between the MST size and the frequency of ex vivo recent activated CD4(+) T cells. In contrast, higher frequencies of recent activated CD8(+) T cells were correlated with a smaller MST size. Moreover, a positive correlation was observed between the lesion total area and the frequency of activated CD69(+) (ex vivo) and CD40L(+) (cultured with Leishmania soluble antigen (SLA)) T lymphocytes. Finally, larger lesions were also correlated with a higher frequency of SLA specific inflammatory cytokine (IFN-gamma or TNF-alpha) producing lymphocytes. These studies demonstrate that immunological markers are correlated with clinical indicators of human leishmaniasis and serve to better understand the evolution of this important parasitic disease.