Plasma levels of the plasma protease inhibitor alpha-2-macroglobulin (alpha 2-M) were followed for 7 days in 90 patients subjected to various surgical procedures. Alpha 2-M was found to decrease strictly in parallel with the decrease seen for haemoglobin and albumin levels in all patients. Changes were most pronounced after extensive operations; total hip replacement (n = 7), pulmonary resection (n = 11), extensive colo-rectal resection (n = 15), and less pronounced after 'minor' operations; mastectomy (n = 23) proximal gastric vagotomy (n = 5) and moderate colo-rectal resection (n = 29). Levels were lowest on the second to third postoperative day, whereafter they slowly returned to normal, preoperative levels during the 7-day study period. Functional and quantitative alpha 2-M levels almost paralleled each other throughout the 7 days studied. Chromogenic peptide substrate assays indicated circulating plasmin-alpha 2-M complexes, while no protease-alpha 2-M complexes could be demonstrated using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) or isoelectric focusing (IEF) analyses. Local accumulation and consumption of proteins within wounded tissues, together with haemodilution, were probably the major factors responsible for the decreased plasma levels seen. It is concluded that the plasma levels of alpha 2-M decrease after major elective surgery strictly in parallel with the decrease seen in haemoglobin and albumin levels, and that circulating plasmin-alpha 2-M complexes are probable. The decrease seems to be graded, that is, proportional to the extent of the operative trauma, similar to the postoperative increase seen in positive acute-phase proteins. Thus, alpha 2-M cannot be used as an internal, unchanged plasma protein standard for other protein changes seen after trauma.