Escherichia coli ribonuclease LS was first characterized as a potential antagonist of bacteriophage T4; the E. coli rnlA gene is required for this activity. When rnlA mutant cells were grown on Luria–Bertani agar containing a high concentration of NaCl, their growth was substantially impaired, and introduction of a mutation into crp or cyaA alleviated the NaCl sensitivity. A mutation in rnlA caused fivefold overexpression of Crp. At the same time, the expression of σ38 was lower by two- to threefold in an rnlA mutant than in the wild type, which probably accounts for the susceptibility to high NaCl concentration. The overproduction of Crp was eliminated by deletion of the Crp-site II, to which Crp binds to enhance its own transcription in the presence of abnormally high concentration of cAMP. Consistently, introduction of a mutation into cyaA also eliminated the overproduction of Crp. In fact, all of CyaA, cAMP and cyaA transcripts accumulated to high levels and, after induction, cyaA transcripts were markedly stabilized in an rnlA mutant compared with the wild type. We conclude that RNase LS regulates Crp–cAMP concentration by degrading the cyaA transcripts.