Isolated lamb hearts were perfused for eight hours at 38± with stroma-free hemoglobin solution (SFHS). The preservation of cardiac structure and function was studied. Control hearts perfused with blood (N = 6) developed no ventricular failure or significant weight gain (13% ± 5), showed no alteration of cellular ultrastructure, and little interstitial edema. Hearts perfused with 7% (N = 7) or 11% (N = 5) SFHS contracted less well, became edematous (22% and 44% weight gain) and showed altered mitochondria, capillary endothelial swelling and hemoglobin extravasation into the interstitial space. The addition of 5–7% albumin to SFHS (N =9) markedly reduced interstitial edema (weight gain 11% ± 13), preserved mitochondria, prevented endothelial swelling, and limited transcapillary escape of hemoglobin. Thus isolated hearts perfused with SFHS develop vascular endothelial damage and an increase in capillary permeability. The addition of plasma proteins to the perfusate protects against this injury.