The circadian rhythms of platelet aggregation in the whole blood and platelet rich plasma-PRP and plasma serotonin were studied in healthy volunteers (n=10) and diabetic patients (type II diabetes mellitus n=12). Platelet aggregation in the whole blood induced by collagen (2 mu g/ml), ADP (1O mu M), arachidonic acid (0.5 mM) and epinephrine (10 mu M), and in PRP induced by collagen (2 mu g/ml), ADP (5 mu M), arachidonic acid (250 mu M), epinephrine (1O mu M) and serotonin-5-HT (1 mu M) was measured at 7:30, 11:30, 17:00, 23:00, 4:00 and 7:00. In healthy subjects collagen- and ADP-induced platelet aggregation in the whole blood was significantly lower at 23:00 and 4:00 when compared to values at 7:30. In PRP normal and diabetic platelet response was the lowest during the night. Diabetic platelets exhibited an enhanced response to 5-HT starting from 17:00 until 4:00 when compared to 7:30. 5-HT-induced platelet aggregation was found to be significantly higher throughout the study in DM patients over controls in parallel to plasma 5-HT. In healthy volunteers plasma 5-HT was higher at 17:00 when compared to baseline values, whereas in DM patients plasma 5-HT was elevated starting from 17:00 until 4:00. An enhanced response of diabetic platelets to 5-HT together with elevated plasma 5-HT levels may contribute, at least partly, to the pathogenesis of diabetic vasculopathy and 5HT(2) receptor blockers may be of value in DM patients.