Extracorporeal membrane oxygenation (ECMO) provides lung rest for moribund infants with congenital diaphragmatic hernia (CDH) after deterioration from a "honeymoon" period. This suggests that unstable pulmonary hypertension determines demise more than pulmonary hypoplasia. We avoided treating overwhelming pulmonary hypoplasia by using ECMO only if the premoribund condition had been marked by evidence of adequate lung parenchyma as a best preductal PO2 greater than 100 torr and PCO2 less than 50 torr with maximal therapy. Twenty-six CDH infants with respiratory distress within 4 hours survived operation. Five were not ECMO candidates, with best PO2 33 +/- 9, PCO2 157 +/- 30 torr, and died. Seven honeymoon infants, with best PO2 325 +/- 80, PCO2 27 +/- 5, survived without ECMO. Fourteen additional infants had honeymoon 26 +/- 13 hours with PO2 256 +/- 48, PCO2 30 +/- 8 followed by a-AdO2 gradients 600 torr x 16 +/- 4.5 hours despite maximal therapy. All 14 were treated with ECMO for 48 to 210 hours. Arterial blood gas values at initiation were PO2 34 +/- 6, PCO2 59 +/- 19, and pH 7.22 +/- 0.2. Right-to-left shunting due to pulmonary hypertension was documented by oximetry and two-dimensional echo/Doppler examination. Twelve of 14 (86%) ECMO-treated infants survived with normal arterial blood gas values on room air, no right-to-left shunting, and no gross neurologic sequellae to date. Two of 14 died. Improvement on ECMO was marked by positive hyperoxia response and decreased right-to-left shunting.(ABSTRACT TRUNCATED AT 250 WORDS)