In former work, intraperitoneal injection of 2-mercaptoacetate (MA), an inhibitor of fatty acid oxidation, increased food intake in rats, which was attenuated by hepatic branch vagotomy, and intraportal injection of MA increased the discharge rate in hepatic vagal afferents. In the present study, we investigated, whether intraperitoneal injection or intraportal infusion of MA affects the hepatic membrane potential in rats in vivo. The liver cell membrane potential was measured in anesthetized Sprague-Dawley rats with the microelectrode technique. Intraperitoneal injection of MA at a dose of 800 micromol/kg body wt significantly decreased the hepatocyte membrane potential by 3.8 mV, whereas at a dose of 400 micromol/kg, the depolarization (1.5 mV) of the membrane was not significant. In another strain of Sprague-Dawley rats, however, MA (400 micromol/kg) produced a significant depolarization of the hepatocyte membrane 50 min (2.6 mV) and 2 h (2.9 mV) after intraperitoneal injection. Intraportal infusion of MA (400 micromol/kg) significantly depolarized the membrane 20 and 50 min after infusion by 3.3 and 4.1 mV, respectively. MA at a dose of 800 micromol/kg also depolarized the membrane (4.8 mV after 50 min). These findings in principle are consistent with the "potentiostatic" hypothesis, postulating a link between the hepatic membrane potential, afferent vagal activity, and the control of food intake.