The function and survival of the autoperfused working heart-lung preparation in the newborn period was studied in six newborn pigs (3 to 5 days old). Normothermic autoperfusion was maintained by a closed blood-primed circuit. Left ventricular afterload was determined by positioning the blood reservoir, and the venous return was adjusted to maintain a right atrial pressure of 6 to 8 mm Hg. Left ventricular function was assessed by a conductance catheter in the left ventricle and was determined by the slope of the end-systolic pressure-volume relationship. Left ventricular diastolic compliance was measured from the end-diastolic pressure-volume relationship. Serial measurements at 60, 120, 180, and 240 minutes showed no change in the end-systolic pressure-volume relationship, whereas there was a significant leftward shift of the end-diastolic pressure-volume relationship after 240 minutes (0.42 +/- 0.02 ml-1 to 0.66 +/- 0.04 ml-1, p less than 0.05). Cessation of effective cardiac function occurred at 268 +/- 10 minutes (+/- SEM). This followed progressive deterioration in pulmonary function based on measurement of arterial blood gases and peak airway resistance. This study shows the feasibility of maintaining systolic cardiac function in a newborn autoperfused working heart-lung preparation. Extended survival beyond 4 hours will require improved methods to preserve left ventricular diastolic function and especially pulmonary function.