The metabolism of Intralipid (intravenously injected) was studied in rats fasted for 48 h. At all doses used, the Intralipid triacylglycerols disappeared rapidly from circulation and concomitantly the hepatic content of triacylglycerols and the level of circulating ketone bodies increased, indicating an active metabolism of Intralipid by the liver. To study this possibility further we used an ultrastructural approach. In rats given Intralipid we detected numerous lipid particles in the spaces of Disse, retained in the interdigitations of the hepatocyte. There were also lipid particles attached to the luminal surface of the endothelial cells. Small lipid particles were seen in close contact with endocytic vesicles internalized into hepatocytes but were present mainly in endothelial cells. Inside the endothelial cells, the endocytic vesicles were detected in contact with lysosomes. Inside hepatocytes, a process of sterification seemed to occur in the endoplasmic reticulum as deduced from the presence of small lipid droplets with ill-defined outlines. Large lipid droplets were seen in close contact with mitochondria, indicating a mitochondrial uptake and metabolism of fatty acids to synthesize and release ketone bodies. The possible role of lipoprotein lipase in the liver for the hepatic uptake of Intralipid particles is discussed.