Marginal zone macrophages are strategically positioned in the marginal zone of the spleen and are thought to play an important role in the initiation of the immune response to T-independent type 2 responses. The cells are characterized by high phagocytic activity and by the selective uptake of neutral polysaccharides. In the mouse marginal zone macrophages react specifically with the monoclonal antibody ER-TR9. Injection of the antibody resulted in a complete abrogation of the uptake of neutral polysaccharides by the cells in vivo, although the cells were still capable of taking up latex and carbon particles. The complete blockade of the polysaccharide uptake did not result in an altered humoral immune response against this antigen. When the antibody ER-TR9 was coupled to the toxin gelonin a complete elimination of the marginal zone macrophages could be established in vivo. However, complete elimination did not result in changes of the immune responses against 2,4,6-trinitrophenylated Ficoll, suggesting that the marginal zone macrophages are either not involved in this type of response, or that their function can be taken over by other cells. The possible role of these cells and the importance of the spleen in the immune response against bacterial antigens is discussed.