Although little glucose is formed from succinate in rat hepatocytes, the rate of gluconeogenesis from monomethyl succinate approaches that from L-lactate. Dimethyl succinate is as good as monomethyl succinate at 5 mM, but not at 20 mM. Monoethyl fumarate and 4-methyl malate are only fair glucogenic substrates, but 1-methyl malate is another good substrate at high concentrations. The esters are apparently taken up either directly through the cell membrane, or by monocarboxylate transporters, and then hydrolyzed intracellularly by some esterase(s). This approach may permit the use of a wider range of substrates and inhibitors for the study of liver cell metabolism.