Amoebae are primitive, actively phagocytosing eukaryotic cells, many of which use bacteria as a major nutrient source. One may suppose that amoebae possess an array of potent antimicrobial molecules acting in synergy to combat bacterial growth inside their phagosomes. Lysosome-like granular vesicles of Entamoeba histolytica contain a family of 77-residue peptides with a compact alpha-helical, disulfide-bonded fold. These polypeptides, named amoebapores, exhibit antibacterial and cytolytic activity by forming pores in membranes of various origin. It is of particular interest that amoebapores are structurally and functionally most similar to polypeptides of mammalian cytotoxic lymphocytes. In addition, amoebic granules contain bacteriolytic proteins with lysozyme-like properties. Some amoebic polypeptides may represent archaic analogs of effector molecules from invertebrates and vertebrates.