The amastigote form of the human pathogen Leishmania mexicana contains high proteinase activity, some 20 times greater than that in the promastigote form and macrophages and appreciably higher than the activity in other flagellate protozoa. The main amastigote enzymes are soluble, whereas those of the promastigote are particulate, and have inhibitor sensitivities characteristic of cysteine proteinases. The very high soluble proteinase activity of L. mexicana amastigotes may be a primary factor in the survival and growth of this mammalian stage in its potentially degradative intracellular habitat.