['Systemic spread of immune activation and mediator release is required for the development of anaphylaxis in humans. We hypothesized that peripheral blood leukocyte (PBL) activation plays a key role.', 'To characterize PBL genomic responses during acute anaphylaxis.', 'PBL samples were collected at three timepoints from six patients presenting to the Emergency Department (ED) with acute anaphylaxis and six healthy controls. Gene expression patterns were profiled on microarrays, differentially expressed genes were identified, and network analysis was employed to explore underlying mechanisms.', 'Patients presented with moderately severe anaphylaxis after oral aspirin (2), peanut (2), bee sting (1) and unknown cause (1). Two genes were differentially expressed in patients compared to controls at ED arrival, 67 genes at 1 hour post-arrival and 2,801 genes at 3 hours post-arrival. Network analysis demonstrated that three inflammatory modules were upregulated during anaphylaxis. Notably, these modules contained multiple hub genes, which are known to play a central role in the regulation of innate inflammatory responses. Bioinformatics analyses showed that the data were enriched for LPS-like and TNF activation signatures.'] Are genomic responses during acute human anaphylaxis characterized by upregulation of innate inflammatory gene networks?