This study used a DNA microarray to examine the genome-wide transcriptional response of *Escherichia coli* to hydrogen peroxide. The microarray, composed of 4,169 *E. coli* open reading frames (ORFs), confirmed that the peroxide response regulator OxyR activates most of the highly hydrogen peroxide-inducible genes. Several new OxyR-activated genes were identified, including *hemH* (a heme biosynthetic gene), the six-gene *suf* operon (involved in Fe-S cluster assembly or repair), and four genes of unknown function. Additionally, several genes, such as *uatA* (encoding mannose hydrolase), showed elevated expression in the *ΔoxyR* mutant strain, suggesting OxyR-dependent repression. The study also found that some genes were induced by hydrogen peroxide in an OxyR-independent manner, indicating the presence of other peroxide sensors and regulators in *E. coli*. For example, the *isc* operon, which is involved in Fe-S cluster formation and repair, was induced by hydrogen peroxide in strains lacking either OxyR or the superoxide response regulators SoxRS. These findings expand our understanding of the oxidative stress response in *E. coli* and highlight the complex regulation of gene expression in response to hydrogen peroxide.This study used a DNA microarray to examine the genome-wide transcriptional response of *Escherichia coli* to hydrogen peroxide. The microarray, composed of 4,169 *E. coli* open reading frames (ORFs), confirmed that the peroxide response regulator OxyR activates most of the highly hydrogen peroxide-inducible genes. Several new OxyR-activated genes were identified, including *hemH* (a heme biosynthetic gene), the six-gene *suf* operon (involved in Fe-S cluster assembly or repair), and four genes of unknown function. Additionally, several genes, such as *uatA* (encoding mannose hydrolase), showed elevated expression in the *ΔoxyR* mutant strain, suggesting OxyR-dependent repression. The study also found that some genes were induced by hydrogen peroxide in an OxyR-independent manner, indicating the presence of other peroxide sensors and regulators in *E. coli*. For example, the *isc* operon, which is involved in Fe-S cluster formation and repair, was induced by hydrogen peroxide in strains lacking either OxyR or the superoxide response regulators SoxRS. These findings expand our understanding of the oxidative stress response in *E. coli* and highlight the complex regulation of gene expression in response to hydrogen peroxide.