The present study was designed to characterize the inotropic effects of ethanol (ETOH) on diabetic rat heart. Left-ventricular papillary muscles, from normal and diabetic (streptozotocin, 50 mg/kg IV; 6 weeks) rats, were superfused with Tyrode's solution at 30 oC while driven at 0.5 Hz. Developed tension, time-to-peak tension (TPT), time-to-90% relaxation (RT90), maximum rate of tension developed (+ VT) and maximum rate of tension fall (-VT) were determined in the absence and presence of clinically relevant concentrations of ETOH (80-240 mg/dl, i.e., 1.7-5.2 mM). Ethanol decreased developed tension, TPT, RT90, and VT in papillary muscles from both groups. Ethanol 80 mg/dl reduced tension, + VT and - VT in preparations from diabetic animals. However, this concentration had no effect on normal muscles. An intermediate concentration of ETOH (120 mg/dl), decreased tension and +VT in preparations from both groups, whereas a higher dose (240 mg/dl) decreased tension, TPT, RT90, VT, and - VT, and induced spontaneous contractures in both groups. The negative inotropic effects of ethanol were generally concentration-dependent and the diabetic myocardium maybe more sensitive to inotropic effects of clinically relevant concentrations of ETOH. Ethanol-induced diminution in contractile tension in normal and diabetic myocardium is associated with reduced contraction and relaxation velocity as well as their respective duration.