Trypanosoma cruzi, the agent of Chagas’ disease, is a parasitic protozoan which presents three cellular forms during its life cycle: epimastigote (extracellular and replicative form in the vector hematophage insect), amastigote (intracellular and replicative form in mammals) and trypomastigote (extracellular non-replicative form in mammals). Sesquiterpene lactones are a group of natural compounds characterized by the presence of a γ-lactone ring and a α-methylene group, displaying diverse biological effects, such as antitumoral and antimicrobial. In this study we have evaluated the effect of two sesquiterpene lactones, dehydroleucodine (DhL) and helenaline (HLN), on T. cruzi epimastigotes. Both compounds inhibit DNA synthesis and reduce protein synthesis, thus clearly affecting cell proliferation (thymidine and leucine-tritiated incorporation means in treated epimastigotes 64.5% and 3.5% respectively, as percentage of control). Additionally, they induce apoptosis as measured by TUNEL (treated 65.4 ± 11.4 % vs control 4.1 ± 1.3 %), and increase the immunoreactivity of caspases 3 and 8, as detected by immuno-western blot (Laemmli, 1970). Apoptosis is a process of cell death in which the cell undergo nuclear and cytoplasmic shrinkage, chromatin condensation, nuclear fractionation, dissipation of transmembrane and mitochondrial potential and finally the disruption of plasma membrane. Among other cations, changes in K⁺ homeostasis are known to lead to the loss of plasma membrane potential. In order to establish the role of potassium plasma membrane conductances in the apoptosis induction process, we have isolated, by differential centrifugation, plasma membranes of T. cruzi epimastigotes (Benaim et al. 1991). The purified membranes were reconstituted in giant liposomes (Riquelme et al. 1990) and their electrophysiological activities were registered by patch-clamp technique (Hamill et al. 1981). This is the first and preliminary approximation to the nature and role of ionic conductance in T. cruzi. Our evidences point to a possible antiproliferative and proapoptotic action of DhL and HLN on T. cruzi at different cellular levels, and open new pharmacological perspectives for the control of the parasite.