In studies to determine the effect of aging on the cell-mediated immune response to Toxoplasma gondii, aged mice showed a delayed onset of macrophage activation during acute infection with T. gondii when compared with young mice of the same strain. Activation appeared to be biphasic, with a peak occurring during the acute infection, followed by a transient decline and then a return to the high levels which are characteristic of the chronic infection. Macrophage activation decreased after approximately 11 weeks of infection in young mice; the decrease was less with increasing age except in the very oldest mice which also exhibited a marked decrease in activation. Specific lymphocyte transformation to Toxoplasma antigen did not reveal any age-related decline during the acute infection. With increasing age during chronic infection, antigen-specific lymphocyte transformation was enhanced except in very old mice. These results suggest that the increased “antigenic load” in older mice (see accompanying paper) with the chronic infection may result in enhanced cell-mediated immunity, but that at the extreme of old age there is a major decline in the inductive mechanism which overrides this stimulation.