The macrophage appears to bind and present antigen to the lymphocyte in the induction and elicitation of the immune response. We have studied the nature of the interaction between dinitrophenyl-guinea pig albumin (DNA-GPA) and macrophage-rich peritoneal exudate cells (PEC) in vitro. PEC from non-immune guinea pigs are not capable of binding sufficient DNP-GPA to induce DNA synthesis in vitro by immune lymphocytes when low (10^-2 µg/ml) concentrations of DNP-GPA are employed although PEC from immune animals function quite well under these conditions. At high antigen concentrations (10⁺² µg/ml) PEC from both immune and non-immune animals function equally well. Incubation of non-immune macrophages in serum from immune animals causes a marked increase in the sensitivity to low antigen concentrations on the part of non-immune PEC. There is a parallel increase in the amount of DNP-GPA bound to the PEC and the degree to which these cells can stimulate immune lymphocytes to divide. This enhanced capacity of PEC to stimulate lymphocytes can be inhibited by DNP-ovalbumin (OVA), a hapten on a heterologous carrier. Also, the binding of DNP-GPA, at low concentrations, to immune PEC can be blocked by anti-immunoglobulin sera. Neither of these agents has a significant effect on the binding of DNP-GPA at high concentrations to immune macrophages or on the binding of DNP-GPA, at either low or high concentrations, to non-immune macrophages. We conclude that there are at least two mechanisms of antigen binding to the macrophage surface. One involves sites of low avidity which are effective only at relatively high antigen concentrations and which appear not to be immunoglobulin. These sites dominate at high DNP-GPA concentration for both the immune and the non-immune PEC populations. In addition, cytophilic antibody, which in hapten-carrier systems is hapten-specific and of high avidity, is present on PEC from immune animals and is the primary means by which small amounts of antigen are concentrated by immune macrophages in quantities sufficient to stimulate lymphocytes.