H-NS is a major constituent of the Escherichia coli nucleoid, whereas sigmaS is a stress-induced sigma factor. An hns null mutation affects the cellular content of sigmaS in such a way that a remarkable accumulation of sigmaS is observed in the logarithmic growth phase, which results in enhanced expression of a number of sigmaS-dependent genes, including the katE gene. We isolated an extragenic mutation that affects the expression of the katE-lacZ fusion gene in the deltahns background. The relevant gene was identified as yhhP, which encodes a small polypeptide of 81 amino acids. Lesion of this gene seemed to affect the stability of sigmaS. A deletion analysis of yhhP revealed that this small protein plays a fundamental role in the general physiology of E. coli. The yhhP-deficient cell is not capable of growing in standard laboratory rich medium (i.e., Luria broth), resulting in the formation of filamentous cells. Homologs of this intriguing protein occur in a wide variety of bacterial species, including archaeal species.