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The natural history of infection with Entamoeba histolytica was studied in 2 slum communities in northeastern Brazil. Twenty-eight index patients colonized with E. histolytica were identified. Three stool specimens from the index patients and their household contacts were gathered over a 45-day period and tested for E. histolytica by means of a specific enzyme-linked immunosorbent assay-based detection kit. The detection kit is an antigen capture assay that has been shown to be highly specific for E. histolytica and does not detect nonpathogenic Entamoeba dispar or other enteric organisms. Blood samples were also collected at the start of the study, at 45 days, and at 6 months and analyzed for E. histolytica-specific antibody. High rates of colonization were seen in the family units. Colonization was self-limited, with 85% of colonized patients clearing their infections within 45 days. Reinfection appeared to be low during this time; however, previous seropositivity did not prevent colonization.