The present study analyzes the effects of zinc on Entamoeba histolytica activity and on its pathogenicity. Metal activity was evaluated in vitro with regard to the parasite's viability, replication, and adhesion to epithelial cells and in vivo with regard to its pathogenicity. The results obtained in vitro show that zinc at 1.0 mM concentration does not affect amebic viability; however, it does decrease amebic replication and adhesion (P < 0.001). In vivo studies performed on a model of experimental liver abscess in the hamster indicate that the intraperitoneal administration of a single dose of zinc at 48 h after the intrahepatic inoculation of amebic trophozoites significantly inhibits (P < 0.001) abscess development. The results indicate that zinc alters the functionality of the ameba in vitro as reflected by a decrease in replication and adhesion and in vivo as manifested by inhibition of amebic pathogenicity.