Enflurane is a direct myocardial depressant and may act as a myocardial protective agent during ischemia. The authors studied the effects of enflurane on myocardial high-energy phosphates and tolerance to ischemia in the normothermic, isolated rat heart. After isolation and perfusion with Krebs-Henseleit buffer, the hearts were perfused with either buffer (control) or buffer gassed with 2% enflurane for 10 minutes. Thereafter, hearts were made globally ischemic and elapsed times to initiation of ischemic contracture (IC) were determined. ATP and creatine phosphate (CP) were measured at the conclusion of control and enflurane administration and at IC. Ten hearts per group were reperfused with buffer following IC for 20 min; peak pressure and ATP and CP were determined. Administration of 2% enflurane significantly decreased peak pressure by 20% but did not alter baseline high-energy phosphate levels nor did it prolong time to IC. However, enflurane-treated hearts exhibited significantly greater (P< 0.01) recovery of function as defined by per cent return of peak pressure (67%±3%) when compared with those hearts not treated with enflurane preischemically (44%±5%). Also, enflurane-treated hearts had significantly higher (P< 0.01) ATP levels at the conclusion of reperfusion than hearts not perfused with enflurane (12.2±.8 μmol/g dry weightvs. 9.0·0.8 μmol/g dry weight). These findings suggest that enflurane administered prior to an ischemic interval enhances postischemic myocardial recovery.