The stress hormone epinephrine produces major physiological effects on skeletal muscle. Here we determined skeletal muscle mRNA expression profiles before and during a 6-h epinephrine infusion performed in nine young men. Stringent statistical analysis of data obtained using 43,000 cDNA element microarrays showed that 1206 and 474 genes were up- and down-regulated, respectively. Microarray data were validated using reverse transcription quantitative PCR. Gene classification was performed through data mining of Gene Ontology annotations, cluster analysis of regulated genes among 14 human tissues, and correlation analysis of mRNA and clinical parameter variations. Evidence of an autoregulatory control was provided by the regulation of key genes of the cAMP-dependent transcription pathway. Genes with known functional cAMP response elements were regulated by the hormone. The impact on metabolism was illustrated by coordinated regulations of genes involved in carbohydrate and protein metabolisms. Epinephrine had a profound effect on genes involved in immunity and inflammatory response, a previously unappreciated aspect of catecholamine action. Information on 526 mRNAs corresponded to genes of unknown function. These data define the molecular signatures of epinephrine action in human skeletal muscle. They may contribute to the understanding of skeletal muscle alterations observed in pathological conditions characterized by sympathetic nervous system overdrive.