Following intrahepatic inoculation of axenic Entamoeba histolytica (strain NIH:200V), all hamsters developed amoebic abscesses in the liver by 7 d after inoculation. All the animals cleared the infection spontaneously by 28 d after inoculation. The establishment of amoebae leading to acute liver abscess was accompanied by significantly reduced levels of antibodies to the plasma membrane (PM) protein of E. histolytica, reduced direct macrophage cytotoxicity, and reduced anti-PM antibody-mediated macrophage-dependent cytotoxicity to amoebic trophozoites. This phase of infection was also accompanied by a significant reduction in cellular sensitization to PM proteins and to phytohaemagglutinin. Reduction in size of the liver abscesses and clearance of infection were accompanied by significant development of anti-PM antibodies, cellular sensitization to the PM proteins, enhanced direct macrophage cytotoxicity, and anti-PM antibody-mediated macrophage-dependent cytotoxicity to trophozoites. The data suggest that the amoebic disease process is modulated by immune responses to the PM protein of E. histolytica.