OBJECTIVE To examine the effects of fructose-1,6-diphosphate on myocardial performance using nuclear scintigraphy. METHODS Prospective, randomized, single-blind, parallel study. METHODS Urban teaching hospital clinical research center. METHODS Individuals with New York Heart Association functional class II-III heart failure (mild to moderate). METHODS Subjects received either intravenous fructose-1,6-diphosphate 125 mg/kg or normal saline 1.3 ml/kg every 12 hours over 10 minutes for four consecutive doses. Left ventricular performance was assessed by radionuclide ventriculography at baseline and within 60 minutes after the fourth infusion. Vital signs were monitored throughout the study period. RESULTS Fructose-1,6-diphosphate resulted in a modest 7% increase in left ventricular ejection fraction (p < 0.05). Peak ejection rate and peak diastolic filling rate did not change significantly. There were no changes in blood pressure or heart rate with either fructose-1,6-diphosphate or placebo. CONCLUSIONS Fructose-1,6-diphosphate produces a modest but significant increase in left ventricular ejection fraction in patients with mild to moderate heart failure.