To study the significance of plasma thrombomodulin (TM) values in diabetes mellitus, we determined plasma TM in 34 patients with non-insulin-dependent diabetes mellitus (NIDDM) men, mean age 54 (SE 2) years. Plasma TM was determined by an enzyme immunoassay with anti-TM monoclonal antibodies. The plasma TM values were significantly greater in NIDDM patients with nephropathy than in patients without nephropathy (P less than 0.001). Also, a significant positive correlation was noted between the concentration of plasma TM and serum creatinine (r = 0.55, P less than 0.001). The plasma TM values of the patients with retinopathy were significantly greater than the values of those without it (P less than 0.002). Furthermore, we noted a significant positive correlation (r = 0.78, P less than 0.001) between plasma TM and the severity of diabetic retinopathy as graded by Scott's classification. These results suggest a close relationship between TM and diabetic microangiopathy.