The contribution of interferon-(IFN-) to immunity from amebiasis was assessed in a three-year prospective study of children 2–5 years of age in an urban slum of Dhaka, Bangladesh. IFN-produced by peripheral blood mononuclear cells stimulated with soluble amebic antigen was measured upon enrollment. Thirty-one of the 209 enrolled children had Entamoeba histolytica–associated diarrhea. Children who produced higher than the median level of IFN-(median 580 pg/mL) had longer survival without E. histolytica diarrhea/dysentery (log rank test P 0.03) and a reduction in the risk of E. histolytica diarrhea/dysentery by more than half (Cox proportional hazard regression 0.45, P 0.04). When adjusted for stunting, the association between IFN-and the time to the first episode of E. histolytica-associated diarrhea remained marginally significant (Cox proportional hazard regression 0.49, P 0.07). We conclude that production of IFN-is linked to nutritional status and predicts future susceptibility to symptomatic amebiasis.