Results of structural studies of colonic mucosal biopsies in acute amebiasis suggested to us the possibility that E. histolytica trophozoites released a cytotoxic substance which damaged cells distant from the organism. Using a tissue culture assay system we detected cytotoxic activity in sonicates of E. histolytica trophozoites grown free of other organisms (axenic culture). The sonicate preparation was also shown to contain enterotoxic activity in a rabbit ileal loop assay. We found that both immune and non-immune serum had a potent antitoxic effect in the assay system, but that non-immune IgG had no effect. Purified immune rabbit IgG prepared with partially purified toxin specifically inhibited the cytotoxic effect. We have now shown that more virulent strains of E. histolytica contain more cytotoxin, that immune IgG from a patient with amebic dysentery is specifically antitoxic, that the toxin is released into the medium during culture, and that the component of serum mainly responsible for the inhibitory effect resides in the alpha globulin fraction. Partially purified toxin preparations have been shown to possess proteolytic activity. Studies continue in an effort to purify the toxin and to better delineate its role in causation of amebic disease.