Myocardial tolerance to total ischemia was compared in animals anesthetized with halothane or isoflurane by measuring the time required for development of cardiac rigor in the absence of coronary circulation or wall stress. Sixteen dogs, eight in each group, were anesthetized with equally potent inspired concentrations of either halothane (2 MAC) or isoflurane (2 MAC), intubated, and ventilated. Thirty minutes later, the heart was rapidly excised. A left ventricular slab was prepared and maintained at 37 degrees C. A portion of each slab was placed in a compressibility gauge that detects rigor onset by an abrupt increase in resistance to tissue deformation. Subendocardial tissue pressure was continuously measured in a second slab using needle-tipped Millar pressure transducers. A third slab was used for intermittent tissue sampling and HPLC assay of high-energy nucleotide levels. There were no differences in pre-ischemic heart rate, mean arterial pressure, glucose, lactate, PO2, PCO2, pH, plasma epinephrine, or norepinephrine levels between the two groups. The onset of rigor as measured by the compressibility gauge was delayed in the halothane group (68 +/- 7.2 vs. 60 +/- 5.0 min; P less than .05). Tissue ATP and ADP levels declined throughout the period of ischemia, with a trend towards preservation in the halothane group. The data show that myocardial tolerance to total normothermic ischemia is improved in animals anesthetized with halothane compared to isoflurane, independent of the effects on hemodynamics or collateral coronary circulation.