The response of neonatal myocardium to ischemia and reperfusion was observed in an isolated working heart model using neonatal rabbits and compared to that of the adult rabbit heart. Lipid peroxidation occurring during ischemia and that occurring during reperfusion were evaluated separately. Malondialdehyde (MDA) in heart tissue was measured as an index of lipid peroxidation, and the occurrence of oxygen free radical damage was assessed by the effects of the scavengers, superoxide dismutase and catalase, on MDA production. Baseline MDA levels were similar in neonatal and adult hearts, were changed little by treatment with normoxic cardioplegia, and were elevated in both groups by treatment with hyperoxic cardioplegia. Thus, the degree of lipid peroxidation during ischemia is similar in neonatal and adult hearts. After 10 min of retrograde reperfusion subsequent to treatment with anoxic cardioplegia, the MDA content of adult hearts was significantly greater than that of similarly treated neonatal hearts. Addition of free radical scavengers to the reperfusion medium lowered the MDA content of adult hearts significantly, but not to the level of neonatal hearts. After 60 min of reperfusion subsequent to hyperoxic cardioplegia, adult hearts had higher MDA than neonates; addition of scavengers to the cardioplegia did not lower the MDA significantly in either group. Only 5 of 12 adult hearts recovered function after hyperoxic cardioplegia, while all 12 neonatal hearts recovered. Our results indicate that neonatal myocardium suffers less damage from oxygen-centered free radicals during reperfusion than does adult myocardium.