Levels of cold insoluble globulin (CIG), also called opsonic alpha2 surface-binding glycoprotein, humoral recognition factor, and fibronectin, are depressed as a result of major trauma. This protein normally promotes the phagocytosis and removal of abnormal particles and bacteria by cells of the recticuloendothelial system. Although CIG depends on macrophages as the effector cells for its opsonic function as is true of both antibody and complement, CIG is neither part of nor dependent on these systems for its opsonic activity. Using a new, rapid bioassay, we have demonstrated that in humans subjected to operative trauma, circulating CIG levels are considerably depressed in the early hours after operation and return to normal within 24 hours. The observed decreases in titer varied in extent, time of onset, and duration. Continuing study is designed to determine potential correlation between initial levels of CIG, decreases in titer resulting from operation, and the incidence of postoperative infection.