p-synephrine and p-octopamine were found to increase lipolysis in adipocytes. The present study approaches the question if these compounds, natural products of the bitter orange (Citrus aurantium fruit), increase lipolysis and fatty acid oxidation in the liver. Experiments were done in the perfused rat liver. Non-recirculating hemoglobin-free perfusion was done using the Krebs/ Henseleit-bicarbonate buffer (pH 7.4) as perfusion fluid. Both p-synephrine and p-octopamine, at the concentrations of 100 μM, were found to stimulate the hepatic triacylglycerol lipase by 40% and 51%, respectively. These seem to be the maximal stimulations possible in the liver. In the perfused liver, p-synephrine, when present at an initial concentration of 500 μM, was able to increase the non-esterified fatty acid release after one hour of recirculating perfusion. The effects of p-synephrine on the oxidation of exogenously supplied [1-14C]octanoate and [1-14C]oleate were minimal. Only oxygen uptake, already stimulated by octanoate or oleate, was additionally increased by the infusion of p-synephrine. These results contrast with those obtained in a previous study with p-octopamine, which increased the production of 14CO2 from both [1-14C]octanoate and [1-14C]oleate. Apparently only the oxidation of endogenous fatty acids is stimulated by p-synephrine. On the other hand, both p-synephrine and p-octopamine stimulate the hepatic triacylglycerol lipase to a much lesser extent than the adipocyte lipase. It can be concluded that p-synephrine affects much more carbohydrate metabolism in the liver than lipid metabolism.