CD163 is a member of the scavenger receptor cysteine-rich family which is expressed exclusively on human monocytes and macrophages. Upon an inflammatory stimulus the protein is shed rapidly from the membranes' surface. CD163 expression is significantly upregulated by glucocorticoids and IL-10. While the membrane-bound form of CD163 was recently identified as scavenger receptor for hemoglobin-haptoglobin complexes, there is no information about a possible role of the shed soluble CD163. It has been suggested earlier that CD163 plays a pivotal role in the downregulatory phase of inflammation. However, it has remained elusive so far as to how this protein might influence the inflammatory process. We have now identified a potential direct anti-inflammatory effect mediated by soluble CD163. The highly purified protein statistically significantly inhibits phorbol ester-induced human T-lymphocyte activation, thus attenuating the immune response to the inflammatory mediator.