The combined use of in vitro culture techniques together with efficient cell separation methods have revealed that macrophages are essential participants in the initiation of some antibody responses (1-4). The experimental design used was to obtain "purified" (macrophage-depleted) lymphocytes by a cell separation procedure and to demonstrate that these cells could not respond to a particular antigen unless macrophages were also present. Several mechanisms of macrophage function during the induction of the humoral immune response have been proposed. Since it was found that in vitro responses to particulate antigens, such as whole erythrocytes, required the participation of macorphages, whereas responses to smaller sized antigens, such as "soluble sheep red blood cell antigen" (3), or polymeric flagellin of Salmonella adelaide (POL) 1 did not, it was proposed that the role of macrophages may therefore be merely to reduce antigenic particles to a smaller and more immunogenic size. Experiments demonstrating that macrophage supernatants enhance responses to erythrocytes (5, 6) are consistent with this simple mechanism of macrophage function. Recently it was found that the immune response to thymus-dependent antigens, even those of small size, such as monomeric flagellin (MON), dinitrophenylated MON (DNP MON), or DNP fowl gamma globulin (DNP F~G), all required the presence of macrophages, whereas responses to the same antigenic determinants (DNP) on polymeric carriers (i.e. POL or DNP POL) which are thymus independent were also found to be