The metabolism offiurazepam-5-14C has been studied in man following catheterization of the portal and hepatic veins. Flurazepam was administered through a tube into the stomach in one patient and into the duodenum in two patients. Thin-layer chromatographs of portal vein blood showed that there was a rapid and early appearance of metabolites offiurazepam consistent with the metabolism of the flurazepam by the intestinal mucosa and at times when the concentrations in the hepatic vein and peripheral blood were very much lower than those in the portal vein. The major metabolites identified in portal vein blood were the mono- and didesethyl metabolites offiurazepam. Considerable hepatic uptake offlurazepam and its metabolites occurred, as evidenced by the lower concentrations of the parent compound and metabolites in the hepatic vein. Thus, “first-pass” metabolism offiurazepam following oral administration occurs in the small bowel mucosa of man as well as in the liver.