Hamano et al. have recently reported that in murine models of amebiasis, innate resistance is associated with nonhemopoietic cells and depends on the activity of interleukin-10. This article raises the issue of the importance of predisposition to amebic colitis and discusses which host factors have a role in innate resistance to invasive disease. Resistance studies that elucidate the mechanisms involved in parasite clearance or parasite invasion are essential to understanding the incidence of amebiasis in humans.