This chapter focuses on the role of the macrophage in removing antigen from extracellular fluids, degrading the larger part of this antigen while presenting a small part of it in persisting immunogenic form. This handling of antigen is done without contributing to the specificity of the immune response, which is determined by the antigenreactive T and B lymphocytes. During the process of uptake of antigen, macrophages appear to retain a few molecules of antigen, undegraded or with few chemical changes. Macrophage-associated antigen becomes an effective immunogenic stimulus mainly in conditions that require two types of lymphocytes to meet with antigen molecules. These lymphocytes are specifically antigen-committed and few in number. The positive immunogenic role of macrophages is related to their capacity to (1) remove extracellular antigen, which might be capable of interacting with and eliminating isolated T or B lymphocytes and (2) retain antigen in lymphoid tissues and promote its necessary meeting with both T and B cells.