The cytopathogenic effect (CPD) of soluble antigens prepared from various strains of Entamoeba histolytica, differing in virulence, was assayed on monolayers of baby hamster kidney cells growing in microtiter plates. Serum-inhibited toxicity could be detected in all these strains and in E. invadens, but not in the Huff strain and in an Acanthamoeba species. Gel chromatography demonstrated a peak activity of the toxin in a fraction with M.W. between 35,000 and 45,000. Other experiments learned that the toxin is a heat-labile glycoprotein, stable between pH 4 and 10, degradable by trypsin, dependent in its activity on sulphydryl goups, and inhibited by anti-E. histolytica IgG and nonimmune serum factors with a M.W. between 50,000 and 100,000. It is also excreted by the ameba and this may explain the effect of serum on contact lysis, induced by intact amebae on BHK cells.