Rabbit alveolar macrophages were infected in vitro with cells of Nocardia asteroides GUH-2 in either logarithmic or early or late stationary phases of growth. Previous studies have established that during the growth cycle dramatic changes occur both in cell wall composition and structure and in the virulence of this organism. This study establishes the correlation between the relative virulence of the phase of growth of the infecting organisms and the degree of inhibition of macrophage phagosome-lysosome fusion. The occurrence of phagosome-lysosome fusion in infected macrophages was determined by both fluorescent and electron microscopy. It was found that relatively few phagosomes containing the highly virulent log-phase organisms had any evidence of lysosomal fusion; more of the phagosomes containing early stationary-phase cells had evidence of fusion. The greatest amount of phagosome-lysosome fusion was observed with the least virulent late stationary-phase cells. Electron microscopic evaluation of infected macrophages indicated that this increase in fusion was not associated with an increase in cell damage. Comparison of macrophages infected with either viable or nonviable organisms indicated that loss of viability did not decrease inhibition of fusion by early or late stationary-phase cells. In contrast, loss of viability did decrease inhibition of fusion by log-phase cells.