Calcium-mobilizing hormones elicit diverse cellular responses by activating plasma membrane receptors coupled to guanine nucleotide regulatory proteins that promote activation of phospholipase C and hydrolysis of polyphosphoinositides. The cleavage products of phosphatidylinositol bisphosphate, inositol 1,4,5-trisphosphate and diacylglycerol, act as primary signals for calcium mobilization and activation of calmodulin-dependent enzymes and protein kinase C. The metabolism of inositol 1,4,5-trisphosphate to several higher inositol phosphates provides additional compounds with potential regulatory actions on calcium movement and cell responses, and the discovery of multiple isomers of protein kinase C reveals a mechanism for diversification and specificity of hormone action among target cells controlled by the same basic transduction system. In addition to its rapid activation by many hormones and neurotransmitters, the calcium-phospholipid signaling system is utilized by several growth factors and oncogenes, consistent with its pervasive role in the control of both immediate and long-term responses of cells to external messenger molecules.