Six strains of Entamoeba histolytica isolated from humans were characterized by their electrophoretic isoenzyme patterns and by virulence in the cecum of Mongolian gerbils (Meriones unguiculatus). Amebae from symptomatic cases of amebiasis were found to belong to zymodeme group II, whereas strains isolated from asymptomatic infections belonged to zymodeme groups I or V. Strains recently isolated from symptomatic cases of amebiasis were highly invasive in the cecum of gerbils. The most prominent pathologic changes present in these infections were the destruction of the interglandular epithelium, crypt hyperplasia and trophozoite invasion of the crypts and submucosa. Strains from asymptomatic carriers were of low or moderate invasiveness in the animal model. Two of the carrier strains expressing a zymodeme group I pattern caused diffuse or transient focal erosions of the interglandular epithelium in some animals. Trophozoites of carrier strains did not invade the crypts nor cause sloughing of the surface epithelium. Presence of colonic lesions was correlated with passage of motile trophozoites in the feces. The severity of histologically demonstrable lesions in the cecum of gerbils was positively correlated with the isoenzyme patterns characteristic of the more virulent amebic strains.