Tissue plasminogen activator (t-PA), tissue plasminogen activator inhibitor, (PAI), and von Willebrand factor (vWF) were measured in 30 diabetics and 17 control subjects. These studies were performed to clarify the role of obesity in causing abnormalities of the fibrinolytic system in diabetics. The t-PA antigen response measured after the infusion of desmopressin acetate (DDAVP) was similar in all groups. Peak responses to DDAVP for controls, type I diabetics, and type II diabetics were 21.2 +/- 9.5 ng/mL, 27.5 +/- 9.0 ng/mL, and 28.8 +/- 11.0 ng/mL (NS), respectively. These responses did not correlate with the body mass index (BMI) or any other of the indices examined. A significant decrease of t-PA activity as contrasted with t-PA antigen following DDAVP occurred in type II diabetics only. The decrease of t-PA activity strongly correlated with greater basal levels of plasminogen activator inhibitor in these same subjects. The plasma level of plasminogen activator inhibitor correlated with BMI but with no other index examined. In contrast to t-PA activity and PAI, vWF responses to DDAVP inversely correlated to basal vWF concentration in all groups. Basal concentrations of vWF were increased in both type I and II diabetics and showed no relationship to degree of obesity. In summary, these results suggest that type II diabetic subjects have decreased t-PA activity, which is best explained by increased levels of PAI. The increased PAI appears related to obesity and not diabetes per se.