Ten patients with dilated cardiomyopathy, 7 ischemic heart disease and 3 idiopathic (7 males and 3 females, mean age 54.8 +/- 11 years), were studied. An insulin euglycemic clamp was performed to evaluate the influence of insulin infusion on cardiac performance. All the subjects were in NYHA functional class II-III and had an ejection fraction < 60% at a previous echocardiographic examination. They were submitted to a noninvasive continuous cardiac output monitoring by variations of thoracic impedance at three stops: a basal evaluation (T0); 1.2 mU/kg/min insulin infusion (T1); 5 mU/kg/min insulin infusion (T2). Moreover at the same times Na+, K+, hematocrit (Hct) and catecholamines were measured in the plasma. The total time required for the study was about 4 hours. Cardiac performance improved as shown by a significant increase in T1 and T2 with respect to the basal condition (T0), of ejection fraction: 57.87 +/- 11.3% (T1) vs 52.25 +/- 14.1% (T0; p < 0.01); 59.5 +/- 10.7% (T2) vs 52.25 +/- 14.1% (T0; p < 0.005); stroke volume: 2.61 +/- 0.5 l/min/m2 (T1) vs 2.01 +/- 0.75 l/min/m2 (T0; p < 0.001); 3.35 +/- 0.66 l/min/m2 (T2) vs 2.01 +/- 0.75 l/min/m2 (T0; p < 0.001) and cardiac output: 41.14 +/- 9.1 ml/m2 (T1) vs 38.83 +/- 7.1 ml/m2 (T0; p < 0.01); 46.45 +/- 8.56 ml/m2 (T2) vs 38.83 +/- 7.1 ml/m2 (T0; p < 0.001). This improvement in cardiac function was not due to an increase in preload because end diastolic volume, Hct, Na+ did not differ through the study. Similarly, afterload measured as mean blood pressure did not decrease. Cardiac function improvement was obtained in the presence of increased catecholamines. In conclusion, exogenous insulin infusion was able, in the presence of euglycemic condition, to improve cardiac performance. This improvement could be due to a direct inotropic effect of insulin perhaps mediated by its metabolic properties on cardiac muscular cells and/or by increasing the cellular intake of Ca+2.