Studies were made on morphological changes of Mycobacterium lepraemurium grown in cultures of mouse peritoneal macrophages. Two types of nonsolid or irregularly stained M. lepraemurium were observed. One type occurred in the growth phase of the organisms during the stage of preparation for bacillary multiplication. The nonsolid bacilli appeared as elongated organisms having pointed ends, isolated acid-fast dots, or faintly stained areas at the ends of the bacilli. It is possible that this irregularity in staining is due to a very gradual, versus an instantaneous, acquisition of acid-fast material during bacillary multiplication and maturation. Solid forms were again observed upon maturation. Nonsolid bacilli were also observed in macrophage cultures infected with autoclave-killed M. lepraemurium. Under these conditions there was an emergence of organisms which showed irregularly stained areas and various forms of deformity unaccompanied by elongation or multiplication. These irregularities were most probably due to the destructive process of digestion of bacillary protoplasm. The present study does not support the current hypothesis that all nonsolid acid-fast organisms are nonviable. Since standard measurements of viability are not applicable to organisms which are noncultivable in vitro, the morphological appearance of human leprosy bacilli has been used for some time to surmise whether organisms are alive, dead, or dying. The idea that bacillary viability can be assessed by the morphological appearance of organisms originated from studies of Rees and associates on the growth of Escherichia coli and Mycobacterium lepraemurium in vitro, on the growth of M. tuberculosis, M. lepraemurium, and M. leprae in mice, and on the morphological changes of E. coli, M. lepraemurium, and M. leprae as observed with the electron microscope (13, 14, 16, 17). Observations made during these studies led them to claim that all solidly stained organisms were alive and all nonsolidly stained ones were degenerate or dead. Our present study on morphological changes of M. lepraemurium grown in macrophage cultures does not support. the contention that all ' Presented in part at the 68th Annual Meeting of the Ameri