Little is known on variations in fatty acid composition of biliary phosphatidylcholine (PC) during acute administration of particular bile acids (BAs) in man. Bile was collected hourly for 5 h in 6 T-tube patients (prereplacement period). Thereafter particular BAs were infused into the duodenum at a rate of 1 g/h for 5 h and bile collected hourly (replacement period). Each patient received two BAs at an interval of 3 days, following a cross-over design. Three patients received deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) and a second 3 patients cholic acid (CA) and chenodeoxycholic acid (CDCA). Bile acid pool contained mainly the two primary BAs in the prereplacement period and more than 80% administered BAs in the replacement period. Hydrophobic and detergent BAs (DCA and CDCA) increased the secretion rates and the percentage of biliary PC species with arachidonic acid and stearic acid; in contrast less detergent BAs (UDCA and CA) did not significantly alter fatty acid composition of biliary PC. Thus, very hydrophobic and detergent BAs would seem to promote the preferential secretion into the bile of lecithin species present in the liver cell plasma membranes, rich in arachidonic and stearic acid.