Although it is clear that macrophages are always present at sites of chronic inflammation their contribution to the evolution of these lesions is not well understood. In vitro studies have shown that macrophages secrete a variety of products on exposure to different stimuli. These include hydrolytic enzymes, active at acid or neutral pH, with known capacity for degrading tissue constituents. Lysosomal acid hydrolases are released from viable cells over a prolonged period of time by various agents known to cause, or are associated with, chronic inflammation. These agents may be nonimmunogenic substances, such as carrageenan and asbestos, which interact directly with macrophages or alternatively the products of immune reactions involving either B or T lymphocytes. These lymphocyte products include immune complexes of certain composition and the secreted products of T lymphocytes stimulated by nonspecific mitogens or specific antigens. In marked contrast biologically inactive substances such as latex particles or digestible substrates such as erythrocytes do not induce the selective release of acid hydrolases from macrophages. It is clear that alghough macrophages secrete abundant amounts of neutral proteinases under certain conditions this release does not occur necessarily during the release of acid hydrolases induced by inflammatory agents. The role played by acid and neutral hydrolases secreted by macrophages during the various stages of chronic inflammatory responses remains to be clarified.