To assess the effects of imposition of moderate diabetes on in vivo cardiac performance in gradually proceeding hypertension, spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY) were treated with streptozotocin (40 mg/kg) or vehicle at 8 weeks of age. Four and 20 weeks later, with the rats under ether anesthesia, peak cardiac output and stroke volume were measured during volume loading and peak left ventricular developed pressure and maximum rate of rise of pressure (dP/dtMaxwere determined during aortic occlusion. Additionally, passive pressure-volume relations were obtained during saline infusion hi potassium-arrested hearts, and the chamber stiffness constant was derived from one exponential function. There was a mortality of 16.1% in the diabetic SHR only. While basal and stressed cardiac performance was unchanged despite the already decreased mean arterial pressure and left ventricular weight at 4 weeks, the diabetic SHR revealed significant decreases in peak cardiac pumping indexes, peak left ventricular developed pressure, and dP/dtMax, with unchanged resting cardiac function, at 20 weeks. Changes seen in the diabetic WKY were reduced left ventricular weight at 4 weeks and reduced peak left ventricular dP/dtMaxat 20 weeks. The chamber stiffness was unaltered with strain or diabetes. These data show that imposition of even moderate diabetes substantially influences the stress-loaded in vivo cardiac performance in the SHR, whereas it produces only minor changes in the WKY.