1. This study examines the effect of propionate, normally produced in the gut, on lipid metabolism of resident macrophage. This cell is very abundant in the epithelial lining of the gut. 2. The activity of propionyl-CoA synthetase in macrophages was shown to be 0.39 nmol/min per mg protein, so this cell presents the ability to use propionate. Propionate at concentrations varying from 0.5 to 5 mM did not affect the activities of carnitine acetyltransferase, ATP-citrate lyase, acetoacetyl-CoA thiolase and 3-oxoacid-CoA transferase. 3. Thus this short chain fatty acid did not alter the capacity for transferring acetyl-CoA from mitochondria to cytosol and for ketone bodies formation and oxidation. However, propionate (40 mM) inhibited the incorporation of [1-14C]-palmitate into phospholipids, cholesterol, cholesterol ester and triacylglycerol and the incorporation of [3-14C]-pyruvate into phospholipids. 4. These findings suggest that fibre-rich diet by generating propionate may regulate macrophage lipid metabolism.