The ability of indole derivatives to facilitate RNA polymerase transcription of the L-arabinose operon in Escherichia coli was shown to require the catabolite activator protein (CAP) as well as the araC gene product. Adenosine 3',5'-monophosphate (cAMP) was not obligatory for araBAD transcription when the cells were grown in the presence of 1 mM indole-3-acetic acid or in the presence of indole-3-acetamide, indole-3-propionic acid, indole-3-butyric acid, or 5-hydroxyindole-3-acetic acid. However, these indole derivatives were unable to circumvent the cAMP requirement for the induction of the lactose and the maltose operons. Catabolite repression occurred when glucose was added to cells grown in the presence of L-arabinose and 1 mM indoleacetic acid or 1 mM cAMP. This effect was reversed at higher concentrations of indoleacetic acid or cAMP. The induction and the catabolite repression phenomena were quantitated by measuring the differential rate of synthesis of L-arabinose isomerase (the araA gene product). These results indicated that indole metabolites from various living systems may regulate gene expression and may be involved in "metabolite gene regulation."The induction of the L-arabinose regulon-araBAD, araE, and araF-in Escherichia coli requires the protein product (P2) of the araC gene, the catabolite activator protein (CAP), and adenosine 3',5'-monophosphate (cAMP) (1-8). Hence, mutants with an inactive product for the crp gene (the gene coding for CAP), the araC gene, or the cya gene (the gene coding for adenylate cyclase) are unable to utilize L-arabinose as a carbon source.The existence of araCl mutants that can circumvent the requirement for cAMP in the induction of the L-arabinose operon (2) and the complexity of various regulatory interlocks (9-11) led to the idea that low molecular weight metabolites other than the ubiquitous cAMP and guanosine 3',5'-monophosphate might function at the genetic level in cell regulation. Recently, we demonstrated with cya deletion strains of E. coli (12) that specific concentrations of imidazoleacetic acid, a compound structurally related to the amino acid histidine, could circumvent the necessity for cAMP in the induction of the araBAD structural genes. In addition, preliminary evidence indicated that a metabolite of tryptophan, indole-3-acetic acid (IAA), could function in the "metabolite gene regulation" of eukaryotic cells and various genera of bacteria. *