This study was designed to determine whether multidose St. Thomas' Hospital cardioplegic solution is as effective for preservation of the immature myocardium during ischemia as it is for the mature myocardium. An isolated working heart model was used. Sets of six hearts from immature (3 to 4 weeks, 500 gm) and mature (24 weeks, 2 kg) rabbits were subjected to 60, 90, or 120 minutes of ischemia. Myocardial protection consisted of infusion of cardioplegic solution every 30 minutes at 4 degrees C in a dose of 10 ml/kg of animal weight and maintenance of hypothermia at 10 degrees C by immersion in a cold saline bath. The percent recovery of preischemic aortic flow was lower in the immature than the mature hearts after 90 minutes (60.3% +/- 7.4% versus 101.8% +/- 4.3%) and after 120 minutes (57.4% +/- 10.6% versus 91.1% +/- 13.6%) of ischemia (results expressed as mean value +/- standard error of the mean, p less than 0.05). There were no differences between the mature and the immature hearts in the recovery of heart rate, left atrial pressure, mean aortic pressure, or glycogen stores. Adenosine triphosphate levels measured at the end of the experiment were not different from control in the immature hearts subjected to 60 or 90 minutes of ischemia, but did decline after 120 minutes of ischemia (18.5 +/- 0.8, 16.9 +/- 1.3, 16.6 +/- 0.6 versus 12.3 +/- 1.8 mumol/gm dry weight, p less than 0.05). Adenosine triphosphate levels in the mature hearts were lower than control in hearts subjected to 60, 90, and 120 minutes of ischemia (18.0 +/- 1.2 versus 13.6 +/- 1.1, 12.8 +/- 0.9, 13.7 +/- 1.5 mumol/gm dry weight, p less than 0.05). Multidose St. Thomas' Hospital cardioplegia does not provide adequate preservation of hemodynamic function in the immature rabbit heart, even though myocardial high-energy stores are well preserved. Additional work is necessary to clarify the mechanism of this finding and to develop appropriate methods for protection of the immature myocardium.