We followed 93 subjects with amebic liver abscess (ALA) and 963 close associate controls at 3-month intervals for 36 months to characterize intestinal and humoral antibody responses to the amebic galactoseinhibitable lectin and to determine whether immunity developed to Entamoeba histolytica or Entamoeba dispar infection following cure of ALA. We found that ALA subjects had a higher prevalence and level of intestinal antilectin immunoglobulin A (IgA) and serum anti-LC3 (cysteine-rich recombinant lectin protein) IgA and IgG antibodies, P < 0.01 and P < 0.05, respectively, compared to controls. The intestinal antilectin IgA antibody response was sustained over a longer time period in ALA subjects (71.8% remained positive at 18 months and 52.6% at 36 months, P < 0.001 compared to 17.6% and 10.3% of controls, respectively). ALA subjects were highly immune to E. dispar infection throughout the study (0% infected at 6 and 36 months, compared to 6.5% and 4.9% of control subjects, respectively, P < 0.05). Upon entry into the study, 6.3% of ALA subjects were infected with E. histolytica; the incidence of new E. histolytica infections in controls (as determined by culture) was too low (1.4%) to determine whether ALA subjects exhibited immunity to new infections. We found that stool cultures every 3 months markedly underestimated the occurrence of new E. histolytica infections, as 15.3% of controls seroconverted after 12 months of follow-up. Unfortunately, under the field conditions present in Durban, South Africa, enzyme-linked immunosorbent assay for detection of lectin antigen in stool yielded unreliable results. In summary, subjects cured of ALA exhibited sustained mucosal IgA antibody responses to the amebic galactose-inhibitable lectin and a high level of immunity to E. dispar infection. Determination of immunity to E. histolytica following cure of ALA will require the use of more sensitive and reliable diagnostic methods.One of the major questions in amebiasis research is whether cure of invasive disease is followed by development of immunity to new intestinal infections and, thus, recurrence of disease. The enteric protozoan Entamoeba histolytica is one of the leading parasitic causes of death worldwide. Disease results from the parasite's ability to invade the colon, causing amebic colitis, or spreading via the portal venous system to the liver, resulting in formation of an amebic liver abscess (ALA). Amebic liver abscesses are more common in adult men and were thought to be fatal if untreated (7). A recent study in Hue, Vietnam, revealed that ALA is even more common than previously realized and may occur frequently in a subclinical manner (10). One large noncontrolled study reported that the rate of recurrence of amebic liver abscesses over 5 years in a highrisk population was less than expected compared to historical controls (14). In a cross-sectional study, the point prevalence of Entamoeba species intestinal infection was lower in subjects who possessed serum antiamebic antibodies (13).The E. histolytica gala...