In Escherichia coli the genes encoding the anaerobic fumarate respiratory system are transcriptionally regulated bg C-4-dicarboxylates. The regulation is effected bg a two-component regulatory system, DcuSR, consisting of a sensory histidine kinase (DcuS) and a response regulator (DcuR), DcuS and DcuR are encoded by the dcuSR genes (previously yjdHG) at 93.7 min on the calculated E. coli map, Inactivation of the dcuR and dcuS gen es caused the loss of C-4-dicarboxylate-stimulated synthesis of fumarate reductase (frdABCD genes) and of the anaerobic fumarate-succinate antiporter DcuB (dcuB gene). DcuS is predicted to contain a large periplasmic domain as the supposed site for C-4-dicarboxylate sensing. Regulation by DcuR and DcuS responded to the presence of the C-4-dicarboxylates fumarate, succinate, malate, aspartate, tartrate, and maleate. Since maleate is not taken up by the bacteria under these conditions, the carboxylates presumably act from without. Genes of the aerobic C-4-dicarboxylate pathway encoding succinate dehydrogenase (sdhCDAB) and the aerobic succinate carrier (dctA) are only marginally or negatively regulated by the DcuSR system. The CitAB two-component regulatory system, which is highly similar to DcuSR, had no effect on C-4-dicarboxylate regulation of any of the genes.