Variation in thepH of biologic fluids parallels modifications in the neutral point of water, which is temperature dependent. Therefore,pH adjustment, when organs from homeotherms are subjected to hypothermia as presently practiced in cardiac surgery or organ preservation, appears to be justified. The present study evaluated, during moderate hypothermia (26° C), the effect of variations in perfusatepH on hemodynamic performance of isolated working rat hearts in conditions of increased workload. Perfusates of blood with apH corrected according to thepH-temperature relationship of neutral water, and blood withpH maintained at 7.4 were used. Hemodynamic function was unaltered by respiratory modifications in bloodpH (normalpH blood:pH = 7.59 ± 0.01; PCO2= 20 ± 1 mmHg; blood maintained atpH 7.4:pH = 7.39 ± 1; PCO2= 37 ± 1 mmHg) and the hypothermic heart perfused with blood atpH 7.4 maintained its ability to do work in response to increased workload. The authors conclude that isolated heart at this degree of hypothermia has the capacity to resist noticeable changes in bloodpH with no deleterious effect on its functional characteristics even at high workloads. The results suggest that the range of optimum extracellularpH value is relatively large at a given temperature. Such good tolerance could be related to tissue buffering efficiency and no conclusion concerning the relationship between tolerance of cellular function and intracellularpH changes can be made.