Primary infection of the large intestine with E. histolytica (amebiasis) is often asymptomatic; however, diarrhea, abdominal pain, and fever may result from invasion and ulceration of intestinal walls. Secondary infection occurs in the liver, lungs, brain, and spleen after the amoebas enter the circulation by way of the portal vein and produce abscesses in these tissues. Encysted E. histolytica are transmitted through food and water, often by fly and cockroach droppings. Excystment (emergence from the cyst) occurs in the vertebrate intestine. The species sometimes is separated by size into the larger, pathogenic form and the smaller, nonpathogenic form, E. hartmanni.

Another species, E. gingivalis, is found around the gum margins, especially in unhealthy or pyorrheic mouths. It has not, however, been shown to cause disease.