We are interested in cellular responses to antigens of parasites to which the cell donor has not been previously exposed and how such responses may influence parasite establishment. In order to characterize such responses we have used cells from unexposed healthy donors and analysed the lymphoproliferative response to various Leishmania aethiopica antigen preparations and the cytokines produced in the process. Peripheral blood lymphocytes were stimulated with SDS-PAGE separated L. aethiopica antigen coupled to nitrocellulose particles. Fifteen of the 16 unexposed individuals tested had proliferative responses to either the whole or/and the antigen-bearing nitrocellulose fractions (NC fractions). Although the degree of response to the fractionated antigen varied in individuals, major stimulatory fractions were found in the high molecular weight region of 110-80 kDa (fractions 3-6) and low molecular weight region of 46-18 kDa (fractions 12-16). Substantial amounts of interferon gamma (IFN-gamma) and interleukin 2 (IL-2) were present in the supernatants of cells stimulated with the whole unfractionated antigen. The potential relevance of such responses in resistance to Leishmania infection is discussed.