In order to explore a possible presence of hyperreactive T-cell clones in human cutaneous leishmaniasis (CL), we have investigated, by flow cytometry, the expression of Vbeta chains of T-cell receptors (TCRs) in the following types of cells: (i) peripheral blood mononuclear cells (PBMCs) from CL patients, which were then compared to those from normal volunteers; (ii) unstimulated and soluble Leishmania antigen-stimulated draining lymph node cells from CL patients; (iii) PBMCs from volunteers before versus after Leishmania immunization; and (iv) PBMCs from healthy volunteers that were primed in vitro with live Leishmania parasites. Our results show a modulation in the TCR Vbeta repertoire during CL and after antigen stimulation of patients' cells. Vaccination, however, leads to a broad expansion of different Vbeta TCRs. We also observed an association between TCR Vbeta12 expression, T-cell activation, and gamma interferon production upon in vitro priming with Leishmania. Collectively, these results both indicate that infection with live parasites or exposure to parasite antigen can modulate the TCR Vbeta repertoire and suggest that TCR Vbeta12 may be implicated in the response to Leishmania.