The function of macrophages in the development of primary plaque-forming cell responses in cultures of mouse splenic lymphoid cells has been investigated. Splenic and peritoneal exudate macrophages are equally efficient in supporting development of responses by splenic lymphoid cells. The active cell in the peritoneal exudate population is a phagocytic macrophage. Macrophages have at least two distinct functions. One is to promote the viability or survival of splenic lymphoid cells in culture; this function can be duplicated by the reducing agent 2-mercaptoethanol. The second function is antigen presentation.