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We tested the hypothesis that the mechanical workload of the heart inversely determines the rate of myocardial edema formation in an isolated, perfused rat heart preparation. Heart rate (HR) was varied in three groups by pacing at 125 (HR125), 250 (HR250), or 350 beats/min (HR350). Left ventricular pressure (LVP) was varied in two additional groups by pacing at 250 beats/min and with the addition of either epinephrine (Epi) or propranolol (Pro) to the perfusate. In five otherwise identical groups, variation of coronary vascular resistance was minimized by adenosine. Myocardial water content (MWC) varied significantly and inversely with HR in the HR125, HR250, and HR350 groups. MWC of the HR250 group was significantly less than that of the Pro group but did not differ from the Epi group. However, when adenosine was used, MWC had significant inverse relationships with HR and LVP. We concluded that the mechanical workload of the heart inversely determines the rate and degree of myocardial edema formation in this isolated heart preparation, and both HR and LVP are determinants of this relationship.