Biliary lipid secretion rates were measured in fed rats after an intravenous injection of Triton WR-1339 (TWR, 60 mg/100 g body wt), an agent that inhibits lipoprotein removal from the circulation. Serum triglyceride, phospholipid (PL), and cholesterol (CH) concentrations rose within 3 h of TWR to 45, 6.6, and 10 times control values, respectively, at 24-36 h. Serum lipids fell rapidly at 48 h and were normal by 72-96 h after TWR. TWR did not alter bile flow, hepatic bile acid transport, or biliary bile acid output. Within 0.5 h of TWR, biliary PL and CH outputs fell greater than 70%, and taurocholate-stimulated biliary PL secretion was markedly reduced. Biliary PL and CH secretion rates were approximately 30 and approximately 40% suppressed, respectively, 24 h after TWR, 160 and 330% elevated, respectively, at 48 h, and normally by 72 h, despite normal taurocholate-stimulated biliary PL secretion. Biliary beta-glucuronidase secretion (a lysosomal enzyme) was unchanged for 3 h after TWR but was increased at 24, 48, and 72 h, independent of biliary lipid secretion. Thus TWR acutely dissociates bile acid from lipid secretion without impairing bile acid transport or biliary lysosomal discharge. Late changes in biliary lipid secretion relate closely to TWR-induced change in serum lipid metabolism but not to stimulation of biliary lysosomal discharge.