Cells from normal non-Leishmania-exposed individuals could respond in vitro by proliferation and interferon-gamma (IFN-gamma) production to Leishmania aethiopica stimulation. The main cell type that appeared to be activated following such stimulation was CD3-, CD16+/56+, i.e. NK cells. Of the few CD3+ cells responding, an involvement of CD8+ cells was evident in the absence of activation of CD4+ cells in normal individuals, while a different feature was observed when patients' cells were investigated. Cells from patients with L. aethiopica infection did not show this NK response, but rather the CD4+ cells were the prominent responding cells. No evidence of the involvement of superantigens or cells utilizing the gamma delta T cell receptor (gamma delta cells) in the response of unexposed individuals was noted.