Recognition and removal is the final common event in the lives of most apoptotic cells in vivo. Macrophages are particularly talented at this task and therefore play a central role in the resolution of inflammation. Because macrophages remove apoptotic cells prior to their lysis, the release of potentially toxic and/or pro-inflammatory intracellular contents is prevented. Uptake of apoptotic cells has more complex benefits than simple removal of noxious substances, however. It was shown by Meagher et al. and then by Stern et al. that uptake of apoptotic neutrophils or eosinophils by human monocyte-derived macrophages did not induce secretion of granulocytemacrophage colony stimulating factor (GM-CSF) or thromboxane B2 [1,2]. This was in marked contrast with necrotic or opsonized cells, which induced both. We subsequently found that apoptotic cells actually inhibited the production of many pro-inflammatory cytokines by macrophages stimulated with either lipopolysaccharide (LPS) or zymosan through an autocrine/paracrine mechanism involving transforming growth factor (TGF)P [3]. Apoptotic cell uptake was found to suppress production of GM-CSF, interleukin (IL)-lP, IL-8, IL-10, and tumour necrosis factor (TNF)a. In contrast with the other cytokines, TGFP levels were increased. By co-incubating LPS, macrophages, and apoptotic cells in the presence of anti-TGFP antibodies, we were able to reverse the suppression of the other cytokines, suggesting that the autocrine production of TGFP was responsible, in part, for the cytokine inhibition we observed. In these studies, we used macrophages which utilized primarily q P 3 and CD36 by which to recognize apoptotic cells; uptake of apoptotic cells by these macrophages was not inhibited by phosphatidylserine (PS) liposomes or by water-soluble PS analogues. We therefore went on to examine the