We have shown that platelets of diabetic patients (D) with coronary artery disease (CAD) produce more thromboxane A2 (TXA2) compared to normal subjects (N), when induced to aggregate with arachidonic acid. The purpose of this investigation was to determine: 1) whether TXA2 biosynthesis in platelets of D without exogenous substrate is increased, 2) whether platelets of D without CAD produce more TXA2 than N and 3) to compare platelet TXA2 biosynthesis in D with those angiographically diagnosed as having CAD but without D. TXB2 (stable metabolite of TXA2) was measured by RIA in platelets of 100 volunteer subjects: 24 D without other clinical complications, 10 D with retinopathy or nephropathy, 7 D with CAD, 30 CAD without D and 11 had D and hypertension. Eighteen subjects had no D, CAD or hypertension. TXA2 synthesis in platelets, stimulated to aggregate with both endogenous and exogenous substrate was higher in all patient classes studied as compared to normal subjects. Plasma triglyceride concentration was higher in diabetics as compared to controls while total cholesterol as well as platelet phospholipid fatty acid distributions were similar in all groups of subjects indicating a similar substrate concentration for TXA2 biosynthesis. It is concluded that platelets of D and CAD with or without D have greater sensitivity to aggregation which might be due to the increased thromboxane synthetase system at one or more sites.