Mechanisms of host resistance to Nocardia asteroides were studied in mice. Two to six weeks after intraperitoneal or intravenous immunization with viable N. asteroides, mice were significantly resistant to intraperitoneal challenge with LD50-100 of N. asteroides in gastric mucin when compared with control (unimmunized) mice (P smaller than 0.03). Resistance could not be transferred to normal mice with serum (1.5 ml administered intraperitoneally) or spleen cells (10-8 cells administered intravenously) from immune donor mice. Peritoneal macrophages from mice immunized with N. asteroides were activated by an in vitro L-cell inhibition assay, and these mice were resistant to challenge with Listeria monocytogenes. Mice with infections caused by Toxoplasma gondii or L. monocytogenes--infections producing activated macrophages--were resistant to challenge with N. asteroides.