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The presence of serum antibodies to Entamoeba histolytica was detected by indirect hemagglutination in a representative sample of the 32 federal entities of the Mexican Republic. This study was designed to include biologic, geographic, social, economic, and educational variables. The total percentage of positive sera was 8.41%. Seroprevalence varied with geographic zones, with the South Central, South Pacific, and Yucatan Peninsula areas showing the highest values (≥ 9%), and the North. Northeast, and Gulf of Mexico areas showing the lowest values (≤ 8.0%). Seroprevalence of anti-E. histolytica antibodies seemed to increase from the northern regions to the southern areas of Mexico. These results indicated that amebiasis is endemic in the Mexican Republic, with areas of high seroprevalence not related to climatic conditions. Exposure to infectious contact with E. histolytica occurred at all ages, with a higher frequency at school age.