The reported work is the first direct ultrastructural comparison of resident peritoneal macrophages from germ-free and conventional animals. Three groups of mice were studied: germ-free (GF), conventionally-reared under isolation conditions (IC), and conventionally-reared in an open environment (OC). The macrophages from the three groups of animals are closely similar morphologically. Particularly noteworthy are the electron-dense, lysosome-like granules which are numerous in the macrophages of germ-free mice and which provide a structural foundation for the presumed microbicidal capability of the phagocytes. Morphometric estimates showed that the "average macrophage" from GF mice is smaller and possesses a smaller, rounder nucleus, a smaller volume fraction of mitochondria and more lysosome-like granules per unit of cytoplasmic volume than the "average macrophage" from conventional mice. Moreover, granules and mitochondria are smaller, on average in the GF phagocytes than in macrophages from conventional mice. The results suggest that peritoneal macrophages from the germ-free mouse represent, more truly than those from the conventional mouse, the nature of the fully differentiated but as yet unstimulated mononuclear phagocyte.