Coronary perfusion has shown that an intramolecularly crosslinked hemoglobin (Hb) with a very low affinity for O2 (Hb crosslinked covalently between the beta chains with 2-nor-2-formylpyridoxal 5'-phosphate, HbXL) has several advantages over ordinary Hb. As predicted from in vitro oxygenation curves, much more O2 was unloaded to the heart at three different heart rates, at two perfusion rates, and when the perfusate was equilibrated with 25% as well as 95% O2. In all cases, the improved O2 unloading occurred at higher tissue O2 pressures than with normal Hb. The greater O2 consumption with HbXL was accompanied by better mechanical performance because, after 90 min of perfusion, the HbXL-perfused hearts maintained two-thirds of their original contractility (dp/dt), while that of the Hb-perfused hearts had declined to one-fifth. A special advantage of HbXL is its ability to unload significant amounts of O2 even at low temperature (10 degrees C), in contrast to whole blood. This should make it useful for supporting aerobic metabolism during low-temperature cardioplegia in cardiac surgery and for organ preservation.