The cytosolic free calcium concentration, [Ca2+]i in phagocytic cells (e.g. neutrophils, human leukemic cell line HL-60) is an important determinant of cellular activity. In resting phagocytes [Ca2+]i is low (approximately 100 nM), but in response to occupation of cell surface receptors, it rises to micromolar levels, thereby activating a variety of cellular functions. The increases in [Ca2+]i consist of two components: an immediate that is independent of extracellular Ca2+, and a more delayed that is abolished by the removal of extracellular Ca2+. These two components reflect the involvement of two subcellular structures in intracellular Ca2+ homeostasis: an intracellular Ca2+ store, referred to as the calciosome; and the plasma membrane. The function of the intracellular Ca2(+)-store depends on a Ca2(+)-pump, functionally and immunologically related to the cardiac sarcoplasmic reticulum Ca2(+)-ATPase, a Ca2(+)-storage protein, similar to muscle calsequestrin, and a Ca2(+)-release channel, which is sensitive to inositol 1,4,5-trisphosphate. The Ca2(+)-regulatory function of the plasma membrane depends on a Ca2+ pump, similar to the erythrocyte-type Ca2(+)-ATPase, and a Ca2+ channel; the activity of the Ca2+ channel is closely coupled to phosphatidylinositol turnover.