Diacylglycerol pyrophosphate (DGPP) is a novel phospholipid identified in yeast, bacteria, and plants, but not yet in mammalian cells. Given its structural resemblance to other phospholipid-activating molecules, such as lysophosphatidate, phosphatidate, and diacylglycerol, it was questioned whether DGPP was capable of activating macrophages to release arachidonic acid (AA) metabolites such as the prostaglandins. It has been found that DGPP is able to potently stimulate prostaglandin production in the murine cell line P388D1 by a mechanism that involves activation of the cytosolic Group IV phospholipase A2 (cPLA2). Our results demonstrate that DGPP possesses macrophage-activating-factor properties and suggest a role for this novel compound in the inflammatory response.