Resident mouse peritoneal macrophages in culture spontaneously secrete lipoprotein lipase. Secretion of lipoprotein lipase was 10-fold greater in thioglycollate-elicited and 6-fold greater in mineral oil-elicited macrophages. The increase in enzyme secretion was dependent on protein synthesis and glycosylation of the newly synthesized enzyme. The addition of 1 to 500 ng per ml of lipopolysaccharide to the culture medium resulted in a dose-dependent inhibition of lipoprotein lipase secretion. Thus, secretion of macrophage lipoprotein lipase is a regulated process, and may be increased as part of the response to inflammation. This may have important implications in the atherogenic process in the arterial wall.