This chapter deals with the information available on Phosphoinositide (PPI) metabolism during stimulation of secretion in macrophages, neutrophils and mast cells, synaptosomes and other brain cells, various adrenal cell types, platelets, exocrine pancreas, and salivary glands. In order to operate as a closed circuit, the PPI cycle has to provide free inositol. A role for GTP, presumably through a G-protein, in the activation of PPI phosphodiesterase has also been suggested from experiments with permeabilized platelets, isolated neutrophil plasma membranes, and rat hepatocytes. Platelet secretion is powerfully inhibited by agents that elevate cyclic adenosine monophosphate levels in platelets and this inhibition is paralleled by inhibition of phosphatidylinositol disappearance and PA accumulation, metabolism of PIP and PIP2, and formation of inositol phosphates. The pancreatic islets, from which the endocrine secretion of insulin and glucagon occurs, also incorporated P into PI and PA during stimulation with carbamylcholine in islets that had been prelabeled with P-orthophosphate.