Macrophages from the mouse peritoneal cavity were examined by electron microscopy at various time intervals up to 24 h after intraperitoneal administration of each of three strains of staphylococci different in virulence for mice: high-virulent, low-virulent, and avirulent strains. After engulfment, avirulent bacteria were highly liable to intracellular digestion, resulting in almost complete degradation within 24 h after injection, whereas high-virulent bacteria were more resistant to digestion, some showing figures suggestive of a dividing process; the gross configuration of most of the ingested bacteria was relatively well preserved over the 24-h period. Time-dependent morphological changes of low-virulent bacteria were intermediate. Among the most distinct cytoplasmic responses to the ingested bacteria was the formation of phagocytic vacuoles around them, the type of which was dependent on the staphylococcal strain infected; ingestion of avirulent bacteria led to formation of vacuoles in which the bacteria were surrounded by a halo of amorphous material of moderate density, which may be the lysosomal content. In contrast, larger vacuoles developed after ingestion of high-virulent bacteria and contained only a small quantity of such amorphous materials. Both types of phagocytic vacuoles were seen around the low-virulent bacteria ingested. Some degenerative changes were found in the macrophages ingesting high- or low-virulent bacteria, but were not in those ingesting avirulent bacteria. Thus, resistance to intracellular degradation, as well as cytotoxicity toward phagocytes of staphylococcal strains, can be correlated with their virulence.