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Fluorescent nanocrystal quantum dots (QDs) are widely used as novel tools in various biological fields including cellular biology, molecular biology, and even in basic and clinical medical fields, due to their far brighter photoemission and photostability. Although many amounts of biological studies, including in vivo experiments, were circumstantially investigated, there is no informative report that investigates whether the QDs affect the mammalian immune system. This study investigated the immune response and biological behavior of QDs in vitro and in vivo. The immune response to QDs by both lymphocytes and kinds of macrophages in vitro and in vivo was investigated. Co-culture of QDs with immune cells showed that apparently normal production of cytokines and chemokines in both mouse CD4+ lymphocytes and peritoneal F4/80+ macrophages (PM phi). In addition, the bionanocomplex of QDs with enhanced-green-fluorescent-protein (eGFP)-encoding nucleotides successfully induced the expression of eGFP protein by PMphi. However, direct injection of QD+nucleotides bionanocomplex aqueous solution into the peritoneal cavity of mice resulted in the inflammation with the infiltration of inflammatory cells into the peritoneal cavity. Furthermore, QD+nucleotides bionanocomplex (but not QD bionanocomplex without nucleotides), induced the production of both proinflammatory cytokines and chemokines by PM phi in vitro. These results indicated that QDs covered with nucleotides caused the peritoneal inflammation in vivo via activation of PMphi and probably nonimmune cells. Taken together, these data indicated that QDs affect the proliferation of immune cells, but not in immune response including cytokine production. We propose here that all nanotechnology researchers should confirm the biological responses of their nanoscale products, because the biological response against nanoscale products can be occurred by not only in immune cells but also other nonimmune cells- - .