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Selective depletion of macrophages from tissues in vivo can be used to investigate whether these cells are playing a role in defined biological processes. This question is particularly relevant to various host defense mechanisms. We have developed a macrophage ‘suicide’ technique, using the liposome mediated intracellular delivery of dichloromethylene-bisphosphonate (Cl₂MBP or clodronate). The method is specific with respect to phagocytic cells of the mononuclear phagocyte system (MPS) for the following reasons: (1) The natural fate of liposomes is phagocytosis. (2) Once ingested by macrophages, the phospholipid bilayers of the liposomes are disrupted under the influence of lysosomal phospholipases. (3) Cl₂MBP intracellularly released in this way does not easily escape from the cell by crossing the cell membranes. (4) Cl₂MBP released in the circulation from dead macrophages or by leakage from …