Two master growth-phase regulatory proteins, H-NS and sigma(S), are involved in the formation of araB-lacZ fusion clones of Escherichia coli MCS2. The stationary-phase sigma factor RpoS is strictly required for the appearance of such mutants, whereas the histone-like protein H-NS represses their emergence. Our results support the idea that genetic changes leading do adaptive mutation in this model system are regulated by physiological signal transduction networks.