Phosphatidylcholine-specific phospholipase C (PC-PLC) catalyzes the hydrolysis of the ester linkage between glycerol and phosphate in phosphocholine (PC) and other phosphatides, such as sphingomylin (SM) and phosphatidylethanolamine (PE). PC-PLC activity has been described in many organisms, from bacteria to mammals. In mammalian cells the enzyme has been found in erythrocytes, lymphocytes, muscular tissue, adipose tissue, and the nervous system. Hydrolysis of PC by PC-PLC results in the production of phosphocholine and diacylglycerol (DAG), a well-characterized lipid second-messenger molecule. The PC-degradation pathway by PC-PLC is activated by many factors, including cytokines, growth factors, mitogens, and calcium ions. Degradation of PC has been implicated in intracellular signal transduction involved in the regulation of cell metabolism, growth, differentiation, and induction of apoptosis. In this review the structure and biological function of mammalian PC-PLC are discussed.