Isolated perfused rat liver is a well-established experimental model for studies on hepatic amino acid and ammonia metabolism. Some aspects and modifications of the liver-perfusion technique are discussed. Perfusion studies with the intact liver have the fundamental advantage that the structural and functional organization of the liver is preserved; however, the experimental system is more complex in view of subcellular and intercellular compartmentation and the recently demonstrated metabolic interactions of different cell populations at the acinar level. These problems of complexity by compartmentation can be largely solved by introducing further techniques such as organ spectrophotometry, the retrograde/antegrade perfusion technique, use of micro-oxygen-electrodes, use of selective inhibitors, radiolabeled compounds, different fractionation techniques of the liver tissue. By means of these approaches, intracellular events can be followed up not only indirectly by analyzing the composition of the perfusate before and after a liver passage, but also directly in the different subcellular and subacinar compartments of a structurally and metabolically intact liver.