The serum concentration of α₂-macroglobulin and that of haptoglobin, the two main components of the electrophoretic α₂fraction, and of α₁-antitrypsin were studied in a series of outpatients with diabetes mellitus. In all age groups a significant increase of α₂-macroglobulin was noted. In adults the increase showed a significant positive correlation with the duration of the disease and was accentuated in the presence of nephropathy with proteinuria. No further increase was noted in the occurrence of other vascular complications. In adult diabetics haptoglobin and α₁-antitrypsin were significantly increased. No correlation was found between the duration of the disease and the concentration of haptoglobin or α₁-antitrypsin. Neither haptoglobin nor α₁-antitrypsin were increased in diabetic children. It is proposed that the concentration of α₂-macroglobulin is more related to diabetes mellitus per se than that of haptoglobin or α₁-antitrypsin, which are increased most in response to complications with inflammatory reaction.