Abstract Cyclic adenosine 3',5'-monophosphate (cyclic AMP) overcomes the repression by glucose of the synthesis of the following inducible enzymes and proteins in Escherichia coli: β-galactosidase, lac permease, galactokinase, glycerokinase, l-α-glycerophosphate permease, Enzyme II for fructose of the phosphoenolpyruvate phosphotransferase system, l-arabinose permease, tryptophanase, d-serine deaminase, and thymidine phosphorylase. Cyclic AMP overcomes the repression by glucose of the synthesis of β-galactosidase in Serratia marcescens F lac, Salmonella typhimurium F lac, Proteus inconstans P lac, and Aerobacter aerogenes; it also overcomes the repression by glucose of galactokinase synthesis in S. typhimurium. A number of analogues of cyclic AMP failed to mimic or inhibit the action of the cyclic nucleotide on β-galactosidase synthesis. Since glucose lowers the intracellular concentration of cyclic AMP in E. coli, we propose that the intracellular level of cyclic AMP regulates the rate of synthesis of many inducible enzymes in E. coli and other microorganisms and that glucose lowers the rate of synthesis of these enzymes by decreasing the intracellular level of cyclic AMP.