Past literature on the pathogenesis of amoebulae is reviewed. Cytochemical and electron microscopy techniques are carried out to investigate the potential Mechanisms of initial cell damage through the interaction between cultivated pathogenic strains of entamoeba histolytica and cell line monolayers. Experiments demonstrated: 1) Contact between the amoeba and cultured cello is essential for pathogenesis to occur. 2) No evidence to suggest that the amoebic enzyme-containing organelles or surface lysosome are responsible for cell dames. 3) No evidence of any amoebic cytotoxic enzyme involvement in cell damage. 4) A toxin , probably plasmalemma associated, that appears to act on the plasma membrane of the contacted cell, leading to the breakdown of selective permeability. Cell lveia results from osmotic effect. The pathological changes in injured cells loading to cell death, and the engulfment of the injured cell by the amoeba by the process of phagocytosis are shown. 3) That cell lysosomes play no part in the early development of cell injury and there is a delay in change in the distribution of the lysosomal hydrolases after the addition of trophozoites. 6) That cell death is not the immediate consequence of viral genome transfer into the host cell, thou/ii the presence of viral genome in the amoeba may have some connection with pathogenicity. The usefulness of cell-line monolayers in evaluating the virulence of cultivated strains of entamoeba histolytica is discussed. Further work to define the chemical nature of the amoeblo plasmalemma is necessary and also to isolate the toxic factor and to determine its role in pathogenicity.