Glucose causes catabolite repression by lowering the intracellular levels of both cAMP and cAMP receptor protein (CRP) in Escherichia coli. The molecular mechanism underlying the down-regulation of CRP by glucose has been investigated. We show that glucose lowers the level of crp mRNA without affecting its stability. Replacement of the crp promoter with the bla promoter almost completely abolishes the glucose-mediated regulation of crp expression. Only a slight reduction in the crp expression by glucose is observed in cya- or crp- strains, suggesting that a CRP-cAMP complex is needed for this regulation. We previously showed that transcription of the crp gene is regulated both negatively and positively. Positive autoregulation of crp is caused by the binding of CRP-cAMP to the CRP binding site II located upstream of the crp promoter. Here we show that disrupting the CRP binding site II essentially eliminates the down-regulation of crp expression by glucose. We conclude that the autoregulatory circuit of the crp gene plays a key role in the down-regulation of CRP by glucose.