The sera of 16 species of wild animals representing 5 classes of vertebrates were assayed for amebicidal activity against species of Naegleria. The greatest activity was observed for sera of bullfrogs, muskrats, and raccoons, all of which are animals associated with water. In contrast, the sera from animals such as toads, box turtles, sparrows, and squirrels exhibited minimal or no amebicidal activity. In general, pathogenic Naegleria tended to be less susceptible than nonpathogenic Naegleria to the lytic effect of raccoon serum. Heat-inactivated serum was not amebicidal, suggesting that perhaps complement may be involved in the serum-mediated lysis of amebas.