Donor availability is a major limiting factor in neonatal heart transplantation. Prolonging donor heart preservation would facilitate distant heart procurement. Forty-two neonatal (1 to 5 days) piglet hearts in seven groups were arrested with cold cardioplegic solutions, stored for 12 hours at 4 degrees C in storage solutions, and reperfused with blood from an adult support pig. The cardioplegic solutions used were a crystalloid solution with potassium chloride 30 mEq/L and bicarbonate (Stanford), the Stanford cardioplegic solution with the addition of calcium (1.2 mmol/L), or an intracellular solution (Sacks) with added glucose. Storage solutions were normal saline, Sacks II, or Sacks II with glucose 20 gm/L. Reperfusion was done with normal blood or modified blood for 20 minutes with superoxide dismutase, catalase, aspartate, glutamate, citrate-phosphate-dextrose, potassium, tromethamine, and 50% dextrose followed by normal blood. Evaluation of stroke work index after 60 minutes of recovery (as percent of control) was performed using the isolated, blood perfused, working heart preparation in all groups: Group I (Stanford cardioplegia, saline storage, normal blood reperfusion) had a recovery of 11%; group II (Stanford + calcium, saline, normal blood) 8%; group III (Stanford + calcium, saline, modified blood, superoxide dismutase 35,000 U/L, catalase 35,000 U/L) 37%; group IV (Stanford + calcium, Sacks II, modified blood, superoxide dismutase 35,000 U/L, catalase 35,000 U/L), 47%; group V (Stanford + calcium, Sacks + glucose, modified blood, superoxide dismutase 35,000 U/L, catalase 105,000 U/L) 89%; group VI (Stanford + calcium, Sacks + glucose, modified blood, superoxide dismutase 150,000 U/L, catalase 150,000 U/L) 107%; group VII (Sacks + glucose, Sacks + glucose, modified blood, superoxide dismutase 35,000 U/L, catalase 105,000 U/L) 115%. CONCLUSIONS The neonatal heart stored hypothermically for 12 hours tolerates normal blood reperfusion poorly. Modified blood reperfusion markedly improves the recovery. Complete functional recovery was achieved by the intracellular Sacks plus glucose storage solution and modified blood reperfusion with oxygen-derived free radical scavengers (high catalase). Extended preservation of the neonatal heart is feasible.