The effect of stevioside, an inhibitor of long-chain fatty acid transport, on ketogenesis and on [14C]CO2 production from [1-14C]palmitate (100-300 microM) was investigated in the isolated and hemoglobin-free perfused rat liver. Stevioside (2.5 mM), a sweet glycoside found in Stevia rebaudiana leaves, inhibited both parameters, but had a lower effect on [14C]CO2 production. At 300 microM palmitate and 150 microM albumin, for example, ketogenesis was inhibited by 66.3%, whereas no significant inhibition of [14C]CO2 was demonstrable. These results were interpreted to reflect 1) different degrees of saturation of the citric acid cycle and the ketogenic pathway and 2) changes in the redox state of the mitochondrial NAD(+)-NADH couple which may also occur upon stevioside infusion.