In vivo clearance of an emulsified triglyceride from rat plasma is strongly influenced by the phosphatidylcholine molecular species and the cholesterol content of the emulsion. Chylomicron-sized, glycerol-tri[9,10-3H]oleate (triolein)-sonicated emulsions containing 2-3 or 9-14 mol% unesterified cholesterol and specific phosphatidylcholines (egg, dimyristoyl, dipalmitoyl, distearoyl) were prepared above the phospholipid gel----liquid crystalline transition temperatures and injected intravenously into awake, non-fasting rats in bolus doses of 1-3 mg lipid. The emulsified triolein was cleared from plasma both by lipolysis during circulation and by uptake of emulsion particles or their remnants into tissues. Increasing the cholesterol content greatly accelerated particle clearance from plasma when emulsions were made with mixed-chain (egg) phosphatidylcholine, but prolonged their circulation time when the emulsions contained saturated phosphatidylcholines. The relative amounts cleared by reticuloendothelial versus liver parenchymal cells were influenced both by the cholesterol content and the phosphatidylcholine species of the emulsions. Significant triolein lipolysis in plasma occurred only with egg or dimyristoyl phosphatidylcholine emulsions containing 2-3% cholesterol and this lipolysis was blocked by increasing the cholesterol content. No lipolysis occurred when emulsions contained dipalmitoyl or distearoyl phosphatidylcholine, irrespective of cholesterol content.