CD163, also referred to as M130, a member of the scavenger receptor cysteine‐rich family (SRCR) is exclusively expressed on cells of the monocyte lineage. In freshly isolated monocytes the CD14^bight CD16⁺ monocyte subset revealed the highest expression of CD163 among all monocyte subsets. CD163 mRNA and protein expression is up‐regulated during macrophage colony‐stimulating factor (M‐CSF)‐dependent phagocytic differentiation of human blood monocytes. In contrast, monocytic cells treated with GM‐CSF and interleukin‐4 (IL‐4) for dendritic differentiation down‐regulate this antigen. CD163 expression is also suppressed by proinflammatory mediators like lipopolysaccharide (LPS), interferon‐γ (IFN‐γ), and tumor necrosis factor α, whereas IL‐6 and the antiinflammatory cytokine interleukin‐10 (IL‐10) strongly up‐regulate CD163 mRNA in monocytes and macrophages. The effects of the immunosuppressants dexamethasone, cyclosporin A (CA), and cortisol differ in their capacity to influence CD163 mRNA levels. Our results demonstrate that CD163 expression in monocytes/macrophages is regulated by proinflammatory and antiinflammatory mediators. This expression pattern implies a functional role of CD163 in the antiinflammatory response of monocytes. J. Leukoc. Biol. 67: 97–103; 2000.