Macrophages have the critical function of presenting antigen in a highly immunogenic form to responding antigen-specific T and B cells in the initiation of antibody responses. The antigen-presentation function and other functions of macrophages that influence lymphocyte behavior in culture have been briefly reviewed. Special attention has been given to genetic restrictions regulating efficient interactions among antigen-bearing macrophages and splenic lymphoid cells in the development of antibody responses to a T cell-dependent antigen. First, genetic restrictions do not govern these interactions in the development of primary antibody responses. Second, immune lymphoid cells develop secondary antibody responses preferentially when stimulated in vitro with antigen on macrophages syngeneic to the macrophages used to immunize the spleen cells in vivo. Third, the genetic restrictions governing macrophage-lymphocyte interactions in secondary responses are controlled by products of the I-A subregion of the H-2 complex. Fourth, the restrictions are antigen-specific and operate at the level of the immune T cell. Fifth, these restrictions involve, at least in part, an active suppressive mechanism. The implications of these genetic restrictions in the regulation of antibody responses are briefly considered.