Phospholipase C gamma (PLC gamma) isoforms are critical for the generation of calcium signals in haematopoietic systems in response to the stimulation of immune receptors. PLC gamma is unique amongst phospholipases in that it is tightly regulated by the action of a number of tyrosine kinases. It is itself directly phosphorylated on a number of tyrosines and contains several domains through which it can interact with other signalling proteins and lipid products such as phosphatidylinositol 3,4,5-trisphosphate. Through this network of interactions, PLC gamma is activated and recruited to its substrate, phosphatidylinositol 4,5-bisphosphate, at the membrane. Both isoforms of PLC gamma, PLC gamma1 and PLC gamma2, are present in haematopoietic cells, The signalling cascade involved in the regulation of these two isoforms varies between cells, though the systems are similar for both PLC gamma1 and PLC gamma2. We will compare these cascades for both PLC gamma1 and PLC gamma2 and discuss possible reasons as to why one form of PLC gamma and not the other is required for signalling in specific haematopoietic cells, including T lymphocytes, B lymphocytes, platelets, and mast cells. (C) 2001 Elsevier Science Inc. All rights reserved.