Microbial cells under growth-limiting stress can generate mutations by mechanisms distinct from those in rapidly growing cells. These mechanisms might be specific stress responses that increase mutation rates, potentially altering rates of evolution, or might reflect non-stress-specific processes in rare growing cells. In an Escherichia coli model system, both frameshift reversion mutations and gene amplifications occur as apparent starvation-induced mutations. Whereas frameshift reversion ("point mutation") requires recombination proteins, the SOS response, and error-prone DNA polymerase IV (DinB), amplification requires neither SOS nor pol IV. We report that both point mutation and amplification require the stationary-phase and general stress response transcription factor RpoS (sigmaS). Growth-dependent mutation does not. Alternative interpretations are excluded. The results imply, first, that point mutation and amplification are stress responses that occur in differentiated stationary-phase (not rare growing) cells and, second, that transient genetic instability, producing both point mutation and genome rearrangement, may be a previously unrecognized component of the RpoS-dependent general stress response.