The indirect hemagglutination (IHA), complement fixation (CF), and agar gel diffusion (Gel) tests were evaluated in the diagnosis and management of amebiasis. Axenically-grown Entamoeba histolytica was used as antigen. A survey of 3,033 patients from our hospital population showed IHA titers indicative of infection in 32 patients (1.1%): 6 had parasitologic or clinical evidence of amebic infection and 10 others had additional serologic evidence of E. histolytica antibodies. Of 345 patients in another study with symptoms suggestive of amebiasis, 85% of 107 with proven infections had positive IHA tests. The three serologic tests were compared in 16 extraintestinal and 127 intestinal cases of amebiasis. All tests were positive in 88% of extraintestinal cases. The IHA test was positive in 95, 61, and 58%, respectively, of invasive, symptomatic and asymptomatic colon cases; the CF test in 85, 56, and 58%; and the Gel test in 86, 54, and 52%. The IHA test was somewhat more sensitive and tended to remain positive longer after cure, but all tests often remained positive for 6 to 12 months, and occasionally for 1 to 3 years. The titer was not helpful in differentiating extraintestinal from intestinal, nor even symptomatic from asymptomatic amebiasis. Skilled judgment is essential in clinical use of these serologic tests.