The basis of bactericidal versus bacteriostatic action of antibiotics and the mechanism of bacterial cell death are largely unknown. Related to this important issue is the essential invulnerability to killing of persisters: cells forming a small subpopulation largely responsible for the recalcitrance of biofilms to chemotherapy. To learn whether death is accompanied by changes in expression of particular genes, we compared transcription profiles of log-phase Escherichia coli treated with bactericidal concentrations of two unrelated antibiotics: ampicillin and ofloxacin. Massive changes in transcription profile were observed in response to either agent, and there was a significant overlap in genes whose transcription was affected. A small group of mostly uncharacterized genes was induced and a much larger set was transcriptionally repressed by both antibiotics. Among the repressed genes were those required for flagellar synthesis, energy metabolism, transport of small molecules, and protein synthesis.