Blood is a valuable clinical sample for high-throughput analysis of gene expression and is likely to become more popular as a diagnostic tool and as a predictive measure of disease progression and drug responsiveness. Gene expression data from blood that has been stored at ambient temperature for greater than 1 h vs. blood samples that have been lysed immediately post-collection shows dramatic changes in relative gene expression for a number of cytokines, chemokines, and transcription factors. Results indicate significant changes in the relative expression of several genes, many of which were either up-regulated or down-regulated, because of storage at ambient temperature: (1) In only 4 h of storage at ambient temperature, greater than 10-fold increases in relative gene expression were observed for interleukin-8 (IL-8), c-myc, and c-fos; (2) Up-regulation of IL-8, a chemokine that mediates inflammatory cell migration, took place only 1-h after collection and increased nearly 100-fold by 4 h; (3) Down-regulation of several anti-inflammatory genes was observed for blood stored at ambient temperature; and (4) A general trend toward selective enhancement of inflammatory responses was observed, mediated by possible mRNA transcription and turnover. These results validate the need for the rapid lysis of whole blood after removal from the source.