We have found that human and rat macrophages express a novel receptor detected by binding of [125I]-CGP 4221, a compound previously considered selective for the Angiotensin II AT-2 receptor subtype. However, Angiotensin II does not recognize the novel receptor. Expression of the CGP 42112 receptor occurs after brain lesions and neuronal death in reat, and in circulating human monocytes and macrophages. Culture of human macrophages with CGP 42112 results in inhibition of production of pro-inflammatory cytokines and secretion of metalloprotein. We are continuing our efforts to clone the novel macrophage receptor form cDNA libraries obtained from human monocytes and from rat spleen.