Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine with numerous immunomodulatory effects, including the inhibition of proinflammatory cytokine production. The mechanisms by which IL-10 exerts these effects still remain largely unknown. As there is evidence that suggests IL-10-mediated cytokine suppression requires the induction of an intermediate gene, we have used gene-chip technology to identify IL-10-inducible genes in human monocytes. We have been able to identify a total of 19 genes that are up-regulated in response to IL-10. Three of these genes had been identified previously: IL-1ra, suppressors of cytokine signaling-3, and CD163; however, the other 16 represent newly identified IL-10-responsive genes. Further analysis of the regulation of eight of these genes showed a remarkable specificity to regulation by lipopolysaccharides (LPS) and IL-10, but not by other anti-inflammatory mediators such as IL-4 and transforming growth factor-beta, suggesting that two diverse stimuli such as IL-10 and LPS may engage common signaling mechanisms.