The recognition of the Entamoeba histolytica galactose-inhibitable adherence lectin by antibodies was studied using sera obtained from subjects in South Africa with an amebic liver abscess or asymptomatically pathogenic or nonpathogenic E. histolytica infection and from uninfected regional controls. In addition, sera from healthy American controls or Americans known to be infected with other parasites were studied. Of the 95 sera containing antibodies to total parasite protein, 95% demonstrated antibodies to the 170-kDa heavy subunit but not to the 35-kDa light lectin subunit. All sera (n = 253) were tested by ELISA for antibodies to lectin: 99% from liver abscess patients and all 4 from individuals asymptomatically infected with pathogenic E. histolytica were positive; all from the 40 healthy American controls and the 29 infected with other parasites were negative (P less than .01). The prevalence of serum anti-lectin antibodies was identical (25%) in asymptomatic South Africans with either a nonpathogenic infection or a negative stool culture for E. histolytica. Thus, the presence of serum antibodies to lectin seems to indicate current or prior invasive amebiasis or asymptomatic intestinal infection with pathogenic E. histolytica.