Cyclic guanosine 3',5'-monophosphate inhibits the synthesis of ,-galactosidase and tryptophanase in cultures of Escherichia coli growing in minimal media with glucose or glycerol as the carbon source. Cyclic guanosine 3',5'-monophosphate acts at the transcriptional level in the lac operon, it exerts its action at the promoter site of the operon, and requires the presence of functional cyclic adenosine 3',5'-monophosphate receptor protein.