Reduced red cell filtration and increased aggregation have been reported in diabetic patients. Heart enlargement is a classical complication of high blood pressure but is also frequently encountered in diabetics. The aim of this work was to explore the relationship between rheological disorders and heart enlargement in diabetics and in an animal model of genetically diabetic rats. 1. Among a series of 92 patients with insulin-dependent or non-insulin-dependent diabetes mellitus, silent myocardial ischemia was evidenced in 28. Coronarography in 24 of these patients was strictly normal in 15. In the patients with angiographically normal coronary arteries, the coronary reserve was perturbed by intracoronary injection of papaverine. The left ventricular mass was normal in 79 patients. In patients with silent myocardial ischemia and angiographically normal coronary arteries, there was a positive correlation between left ventricular mass and red cell filtration index using the Hanss hemorheometer (n = 8, r = 0.954, p = 0.001). 2. Red cell stiffness was studied sequentially from 3 to 18 months in diabetic rats Goto Kakisaki (GK). In these rats, cardiac index (heart weight/body weight) was significantly higher than that in Wistors control rats (0.27 +/- 0.02% vs. 0.17 +/- 0.01%, p < 0.001) and was significantly correlated with erythrocyte magnesium (r = 0.920, p 0.026). Overall, the cardiac index in the rats was significantly correlated with red cell filtration (r = 0.370, p = 0.044). In GK rats, heart rate was significantly slower and systolic blood pressure was slightly higher than in control rats (telemetric measures). These findings show that in diabetes mellitus, heart enlargement may be determined by factors other than hypertension or sensitivity to sympathetic stimulation and might be favored by rheological changes and/or excessive intracellular magnesium. In patients with diabetes, the reduced coronary reserve could result in left ventricular hypertrophy but also rheological changes.