To study the role of macrophages in immune and non-immune defence mechanisms, a new technique to eliminate macrophages has been developed. This technique uses the capability of macrophages to ingest and digest particulate compounds. As particulate compound liposomes with entrapped clodronate are used. Macrophages will ingest these liposomes and after fusion of their endosomes with their lysosomes the bilayers are disrupted under influence of phospholipases and the clodronate is released into the cytoplasm. If the intracellular concentration of free clodronate reaches sufficiently high values, the macrophage will die. The applications of the approach and some of the results obtained up to now using this macrophage 'suicide' technique are discussed.