Aging is often associated with decreased myocardial ischemic tolerance. We recently reported that chronic preconditioning produced by continuous exposure to morphine affords a profound cardioprotective phenotype in young mice. In this study, we determined if chronic exposure to morphine retained its ability to precondition the myocardium in the young or aged heart. Young (10-14 weeks) or aged (24-26 months) C57/BL6 mice were untreated, administered morphine acutely (30 microM), or implanted with a morphine pellet (75 mg) for 5 days prior to heart isolation and perfusion. Following equilibration, perfused hearts were subjected to 25 min ischemia and 45 min reperfusion. Untreated hearts from both young and aged mice displayed marked contractile dysfunction and LDH release following reperfusion. Acute infusion of morphine improved recovery of end-diastolic pressure and developed pressure in young (P < 0.05 vs. untreated) but not senescent hearts. Hearts from mice exposed to morphine for 5 days displayed a further improvement in post-ischemic contractile function (P < 0.05 vs. acute treatment), and a marked reduction in post-ischemic LDH efflux (P < 0.05 vs. untreated) in both young and senescent hearts. These data demonstrate that aged hearts maintain the ability to be preconditioned by chronic exposure to morphine in the absence of acute protection.