The phagocytic and metabolic functions of the reticuloendothelial system (RES) were determined, by measuring the plasma clearance rate of125I-labelled microaggregated human serum albumin and the increase in plasma metabolites of this test substance, in patients with chronic renal failure and in renal transplant recipients at different times after transplantation. All transplant recipients received triple immunosuppressive therapy consisting of azathioprine, corticosteroids, and antilymphocyte globulin. The intravascular clearance of microaggregated albumin was significantly depressed in patients when tested at 1 to 12 days(P< 0.001), 1 to 4 months(P< 0.02), and 6 to 9 months(P< 0.001) after transplantation compared to pretransplantation. The 1− to 3-year transplant survivors had a normal RES phagocytosis. Furthermore, the metabolic RES function in all groups of transplant recipients except the group of patients tested at 1 to 4 months after transplantation was significantly impaired compared to pretransplantation.Administration of antilymphocyte globulin and extremely high daily doses of steroids were probably responsible for the significant depression in the RES functions recorded immediately post-transplantation. The further development of the phagocytic ability of the RES was shown to be correlated to the cumulative dose of steroids given over the last 12 months. The azathioprine regime seemed to have no influence on the RES functions.The RES is a major host defence mechanism against bacterial and viral infections(1–4)and tumour growth(5–7). Macrophage phagocytosis and metabolism are also important in the induction of an immune response to foreign antigens(8–10)and in the rejection of allografts(11, 12). Depression of the RES function induced by various agents (methyl palmitate, trypan blue, silica, carrageenan, or antimacrophage serum) was shown to prolong the survival of organ as well as tumour grafts(13–17). On the other hand, glucan-induced stimulation of the RES was associated with enhanced rejection of both tumour and bone marrow transplants(14, 17).Immunosuppressive agents such as azathioprine, corticosteroids, and antilymphocyte serum, used in transplantation surgery to suppress the immune response, have been reported to impair RES phagocytosis(18–21). Several investigations have been made in animals and some in man on the capacity of the RES to clear various colloids and lipid emulsions from the circulation(22–25). In recent years, moreover, methods have been developed for the determination of not only the phagocytic but also the metabolic function of the RES(26–28). Those used most frequently utilize a rapidly metabolizable RES test substance of microaggregated human serum albumin labelled with radioactive iodine, a substance which can safely be used in man(26, 28).The purpose of the present study was to determine both the phagocytic and the metabolic functions of the RES in patients undergoing renal transplantation during immunosuppressive therapy. As RES test substance, microaggregated human serum albumin labelled with125I was used.