Accelerated atherosclerosis is commonly observed in diabetes mellitus as well as in some kidney diseases. This may be partly due to platelet hyperactivity. Serotonin (5-HT) is thought to play a role in platelet/vessel wall interactions and to be implicated in the pathogenesis of atherosclerosis. The aim of the study was to evaluate platelet aggregation and peripheral serotonergic system in patients with diabetic nephropathy. The studies were performed in 37 patients with diabetic nephropathy (age 53.5 +/- 14.9) and healthy volunteers (age 44.2 +/- 12.3). Platelet aggregation (in PRP according to Born) induced by collagen (2 micrograms/ml), ADP (5 microM), epinephrine (10 microM) arachidonic acid (0.25 mM) and 5-HT (1 microM) was found to be significantly enhanced in diabetic relative to controls. Whole blood 5-HT was significantly lower in diabetics patients, whereas plasma 5-HT was significantly higher in diabetic patients when compared to controls. Since serotonin can amplify platelet aggregatory responses to various agonists, platelet hyperactivity in diabetes may be in part due to an enhanced availability of this amine. Disturbances in peripheral serotonergic system together with platelet hyperaggregability may be associated with an increased incidence of cardiovascular complications in diabetes.