In a random sample of 200 patients with type 2 diabetes mellitus, immunoreactivities to ACE (angiotensin converting enzyme) were measured by ELISA. Immunoreactivities were positive for 129 (64.5%) patients, and were positive in 30 (83.3%) out of 36 patients in the early stage of clinical diabetic nephropathy. Serum ACE activity in rabbits immunized with ACE decreased to 50% of the control level after 7 months (78.0 +/- 3.8 IU/L/37 degrees C, basal, 42.0 +/- 5.0 at 7 months and 33.3 +/- 3.5 IU/L/37 degrees C at 8 months, respectively). When rabbit serum containing antiACE antibodies was mixed, after heat-treatment at 56 degrees C for 30 min, with normal human serum, the ACE activity was reduced in a concentration-dependent manner. These results suggested that anti-ACE autoantibody may be present in patients with type 2 diabetes mellitus. However, the absence of data on the epitope for the antibody does not allow any conclusion except that the immunoreactivities to ACE are higher in type 2 diabetic patients than in non-diabetic individuals.