Concanavalin A (ConA) and pokeweed mitogen (PWM) were injected intraperitoneally into mice and the effects on peritoneal macrophages were evaluated. When compared with saline injected controls, both mitogens caused at 4 days following injection a two-fold increase in the yield of macrophages, and these macrophages spread more rapidly on glass. Also, a higher percentage of heat-killed Candida albicans ingested by these macrophages stained red with neutral red dye. ConA, in contrast to PWM, produced a rapid, transient fall in macrophage yield within the first 3 h after injection. This effect could not be attributed to a direct agglutinating activity of the mitogen. Furthermore, only ConA resulted in the appearance of macrophages with an increased ability to phagocytize rabbit red blood cells in a serum-free medium.