A group of 42 patients hospitalized with either amebic liver abscess or amebic dysentery were skin-tested with an extract of Entamoeba histolytica. Of these patients 81.1% were positive; 14.1% of a comparable asymptomatic group of 78 cases were reactive. Among the patients with invasive clinical amebiasis, hypersensitivity was more frequently of the immediate than the delayed type. In the group without symptoms attributable to E. histolytica, most skin reactions were of the delayed type. Indirect tests for hypersensitivity and in vitro serologic reactions were carried out on both groups. The passive cutaneous anaphylaxis (PCA) test in the monkey was insensitive. Fair agreement was obtained among positive skin tests in man, PCA reactions in the guinea pig, and hemagglutinin and fluorescent-antibody titers. Although the increased sensitivity of the indirect hemagglutination test may result in difficulty in clinical interpretation in communities in which amebiasis is hyperendemic and a disease problem, all three serologic tests could be of value as diagnostic aids as well as in epidemiologic investigations.