The interaction between virulent and less virulent strains of Nocardia asteroides and cultured rabbit alveolar macrophages was studied. It was shown that cells of the less virulent strain (N. asteroides 10905) were rapidly phagocytized and destroyed. However, some cells were able to avoid being killed, and they persisted within the macrophage in an altered, gram-negative form. These variants apparently increased in numbers after several days within the macrophage population, so that at 9 days postinfection more colony-forming units per macrophage were recovered than at 3 h. Little or no extracellular growth was observed in the tissue culture medium. During the increase at 9 days, both transitional-phase variants and L-forms of N. asteroides were isolated from the macrophages but not from the medium. Gram-positive bacterial cells were never observed in 9-day infected macrophages. In contrast, cells of the more virulent strain (N. asteroides 14759) were not destroyed after being ingested. After 6 h postinfection, it was observed that the number of colony-forming units per macrophage had increased significantly. There was no corresponding increase in extracellular organisms observed in the culture medium. Therefore, cells of N. asteroides 14759 were able to grow rapidly within cultured rabbit alveolar macrophages. Upon continued incubation of the infected cells (24 h postinfection), it was shown that this strain of Nocardia grew out of the macrophages as acid-fast branching filaments. From these data, it is clear that the initial interaction between N. asteroides and unstimulated, nonimmune alveolar macrophages depends upon the relative virulence of the nocardial strain.