Trypanosoma cruzi epimastigotes were subjected to the lysosomotropic agents L-leucine methyl ester and ammonium chloride to determine their effects on the ultrastructure of the parasite. The lysosomotropic agents applied to epimastigotes caused a time-dependent alteration in the morphology of the cells marked by a 5-fold increase in the number of lysosomes. Continued exposure to ammonium chloride caused slight disruption of the reservosomes. The amino acid ester, however, while causing the parasite to swell after prolonged exposure (e.g., 24 h), had little effect on the reservosomes, the kinetoplast, or even the mitochondrion. A specific inhibitor of cysteine proteinases provided some protection for lysosomes from the effects of the amino acid ester. Although it is agreed that reservosomes are similar to endosomes, no lysosomal fusion with the reservosomes was observed. Acid phosphatase activity was observed only in lysosomes.