A set of quantitative signs of activation, previously developed in studies of inflammatory peritoneal macrophages, has been applied to the study of immunologically stimulated peritoneal cells. Mice that are infected systemically with Bacillus Calmette Guérin (BCG) and then challenged locally with soluble mycobacterial antigens generate populations of cells that spread rapidly in culture, display an elevated pinocytic rate, ingest IgMC-coated sheep erythrocytes, and have diminished levels of 5′-nucleotidase activity. These effects depend on sensitization with live organisms, require secondary antigenic challenge, and develop on the same schedule as does effective cell-mediated immunity. The challenge is antigen specific and cannot be replaced by a nonspecific inflammatory stimulus. Thus, the characteristics of inflammatory macrophages that were previously defined are applicable to the study of immunologically mediated macrophage activation. Cells sharing this pattern of characteristics, whatever their mode of generation, are proposed to represent a distinct class of differentiated macrophages, as compared with the resident macrophage population.