Clinical studies have shown that the ability of aspirin to prevent cerebrovascular accidents is weaker in patients with diabetes. The aim of this study was to determine whether high concentrations of glucose modified the effect of aspirin, ticlopidine and clopigodrel on platelet function and platelet-subendothelium interactions. This in vitro study tested three different concentrations of glucose. The effects were analyzed by comparing platelet aggregometry in whole blood, nitric oxide and prostacyclin production in cultures of human endothelial cells, and by quantitative analysis of morphological features of the platelet-subendothelium interaction under flow conditions. High concentrations of glucose increased platelet aggregation (13.9 Omega with 5 mM glucose vs. 21.6 Omega with 16.6 mM) and platelet-subendothelium interactions (28.9% with 5 mM glucose vs.35.2% with 16.6 mM), and decreased nitric oxide and prostacyclin production. In the presence of high concentrations of glucose, the antiaggregant effect of aspirin and its influence on nitric oxide production were diminished (IC50 54 microM with 5 mM glucose vs.556 microM with 16.6 mM glucose), and its effect on the platelet-subendothelium interaction was reduced (10.5% platelet occupancy with 5 mM glucose vs.23% with 16.6 mM glucose). The effects of ticlopidine and clopidogrel were not significantly modified.