Platelets obtained from some diabetic patients show enhanced in vitro platelet aggregation. This study sought to determine whether platelets obtained from diabetic subjects synthesize increased quantities of the labile aggregating substance. TXA2, and whether it may play a role in the enhanced platelet aggregation. Arachidonic acid (1 mM)-stimulated TXA2 synthesis, as determined via radioimmunoassay of its stable metabolite TXB2, was significantly greater (p < 0.01, n = 12) in platelet-rich plasma obtained from diabetic patients than in matched controls. Arachidonic acid-stimulated TXB2 synthesis in the diabetic platelet-rich plasma was positively correlated with the ambient fasting plasma glucose (r = 0.61, p < 0.02, n = 15). Platelet aggregation induced by arachidonic acid (0.4 to 0.8 mM) was inhibited significantly less than in matched controls by imidazole, a thromboxane synthetase inhibitor (p < 0.01, n = 11), and 13-azaprostanoic acid, an antagonist of the actions of PGH2 or TXA2 on platelets (p < 0.04, n = 14). We conclude that platelets obtained from some diabetic subjects manifest increased synthesis of TXA2, which may contribute to the enhanced platelet aggregation.