The intravascular injection of contrast medium produces a rise of ventricular filling pressure which may reflect blood volume expansion, a negative inotropic effect on the myocardium, and/or a decrease in ventricular diastolic compliance. This phenomenon was studied by randomly infusing three substances, Renografin-76®, 1% saline and 38% sucrose, into the aortic root of the isolated perfused canine heart. The preparation was modified by having an inflated balloon within the left ventricular cavity so that the end diastolic ventricular volume and afterload were fixed. A dose-related depression of left ventricular systolic pressure and peak dP/dt due to contrast media occurred, without a significant change in the left ventricular diastolic pressure. This decrease in ventricular contractility due to Renografin-76 could not be attributed entirely to either a saline or an osmotic effect. No significant changes were observed in left ventricular diastolic compliance. Sucrose was found to exhibit a marked positive inotropic effect.