The phagolysosome is an antimicrobial and degradative organelle that plays key roles in macrophage-mediated inflammatory and homeostatic functions. Whereas mature phagolysosomes are known to sequester and degrade their contents into basic nutrients, they were not previously assigned an active role in amplifying inflammation. We have described a novel macrophage process in which partially digested immunostimulatory PAMPs are released extracellularly from the mature phagolysosome via discrete events we term eructophagy. Eructophagy is induced by proinflammatory stimuli, negatively regulated by IL4 and MTOR, and is dependent on key autophagy proteins, including fusion machinery of degradative and secretory autophagy. We propose that macrophages use eructophagy to release processed PAMPs/DAMPs to amplify local inflammation.