To identify Bombyx mori genes involved in the early response to injury and microbial challenge, we performed genome-wide gene expression-profiling experiments using oligonucleotide DNA microarrays. Of approximately 23,000 genes examined, 465 displayed changes in mRNA expression levels. Of these, 306 were induced and 159 were repressed in response to injury (injection with phosphate buffer saline) or challenges by Gram-negative (Serratia marcescens), Gram-positive bacteria (Staphylococcus aureus), or fungus (Beauveria bassiana). Many of these differentially expressed genes can be assigned to specific functional groups of the innate immune response, including recognition, signaling, melanization and coagulation, and antimicrobial peptides. Seventeen percent of differentially expressed genes encode proteins with no obvious similarity to known functional domains. Of particular interest is a member of the juvenile hormone-binding protein family, which was highly induced by both injury and microbial challenges. The possible role of juvenile hormone in innate immunity is discussed.