Since certain reports in the literature suggested utilization of plasma free fatty acids (FFA) by intestinal mucosa, a study was undertaken to investigate the mucosal metabolism of plasma FFA in rats. Two minutes after i.v. injection of 14C-palmitic acid, mucosal radioactivity was 1% of the administered radioactivity. Of mucosal radioactivity 42% was in water-soluble metabolites, 28% in phospholipids and only 16% in triglycerides. The use of dual labelling revealed marked differences in the metabolism of palmitic acid entering the intestinal mucosa simultaneously from the lumen (3H-palmitic acid) and plasms (14C-palmitic acid): whereas limitlasms (14C-palmitic acid): whereas luminal palmitate was chiefly esterified to triglycerides, plasma palmitate was preferentially oxidized and incorporated ino phospholipids. Villi did not differ from crypts in this regard, indicating that the intestinal metabolism of long-chain fatty acids depends on the site of entry into epithelial cells. Glucose administration did not affect the intestinal metabolism of plasma FFA. However, intraduodenal ethanol inhibited mucosal oxidation of plasma FFA by 60% and simultaneously increased incorporation into triglycerides twofold. During fat absorption the uptake of plasma FFA into intestinal mucosa doubled.