Recent studies show that brief exercise alters circulating neutrophil and PBMC gene expression ranging from cell growth to both pro-and anti-inflammatory processes. These initial observations were made solely in males, but whether peripheral blood mononuclear cell (PBMC) gene expression is altered by exercise in females is not known. 10 early pubertal girls (8-11 y.o.) and 10 late pubertal girls (15-17 y.o.) performed 10, 2-min bouts of cycle ergometry (~90% peak HR) interspersed with 1-min rest intervals. Blood was obtained at rest and after exercise and microarrays performed in each individual subject. RNA was hybridized to Affymetrix U133+2.0 Arrays. Exercise induced significant changes in PBMC gene expression in early (1320 genes) and late (877 genes) pubertal girls. The expression of 622 genes changed similarly in both groups. Exercise influenced a variety of established gene pathways (EASE<0.04) in both older (6 pathways) and younger girls (11 pathways). Five pathways were the same in both groups and were functionally related to inflammation, stress, and apoptosis such as: Natural killer cell mediated cytotoxicity, Antigen processing and presentation, B cell receptor signaling, and Apoptosis. In summary, brief exercise alters PBMC gene expression in early and late pubertal girls. The pattern of change involves diverse genetic pathways, consistent with a global danger-type response, perhaps readying PBMCs for a range of physiological functions from inflammation to tissue repair that would be useful following a bout of physical activity.