A widespread, but incorrect, view of the neutrophil portrays it as a short-lived, terminally differentiated cell that has a highly condensed nucleus and hence is unable to induce gene expression. However, these cells express mRNA encoding phagocytic receptors, modulate RNA synthesis in response to lectin stimulation or glucocorticoid treatment, and upregulate genes involved in phagocytic function, such as respiratory burst activity and cytokine secretion. Most studies of neutrophil gene expression have examined cytokine stimulation and have focused on a few specific genes of known interest, rather than the global genetic repertoire of the cell. In part stimulated by the availability of gene and expressed sequence tag databases, several approaches have been developed to assess the levels of all mRNA species found in single RNA preparations. We have analyzed the regulation of gene expression in neutrophils using a gel-based method that displays 3 end fragments of cDNA generated by restriction enzymes. Our data indicate that neutrophils are capable of extensive, rapid, and complex changes in gene expression, involving at least several percent of all mRNAs present in the cell. The number and magnitude of mRNA responses are comparable to those measured on activation of normal T cells. The data also indicate that activated neutrophils are a source of newly synthesized, physiologically significant, intercellular signaling molecules. Curr Opin Hematol 2000, 7: 16–20© 2000 Lippincott Williams & Wilkins, Inc.