We have used the calcium indicator, Fura-2, to investigate cytosolic calcium responses to cross-linking of monomeric IgG-occupied surface Fc gamma receptors (FcγR), using populations of the human monocyte-like cell line, 0937. The magnitude and duration of the calcium response observed, and the relative contribution to the response of internal stores and external calcium, are found to depend on the state of differentiation of these cells. Initial release of calcium from stores following FcγR cross-linking is enhanced by prior treatment of U937 cells with both interferon-γ, and, to a lesser extent, with dibutyryl cAMP. A large and prolonged entry of external calcium is observed in dibutyryl cAMP treated cells; this may be due to direct regulation of calcium channels by the low affinity receptor, FcγRII (whose expression is up-regulated in these cells), since the smaller and more transient entry observed in Interferon-γ treated cells, (where the high affinity receptor, FcγRl, is up-regulated) argues against a common pathway of store-mediated calcium entry.