We exposed 128- to 130-day-gestation fetal lambs by cesarean section leaving the umbilical cord and placenta undisturbed, and we then treated the lungs with pulmonary conditioning (i.e., repeated prolonged inflations to 35 cm H2O, followed by a continuous positive airway pressure of 15 cm H2O). To investigate the added effect of pulmonary vasodilation upon the increase of total compliance and pulmonary oxygen uptake, we also administered acetylcholine intravenously at a rate of 80 micrograms min-1. Eleven of 13 lambs met the endpoint criteria of either compliance (0.5 ml [cm H2O]-1 kg-1; 1 animal), or pulmonary oxygen uptake (6 ml kg-1 min-1; 6 animals), or both (4 animals), and were delivered within 0.6 +/- 0.3 h. This time was significantly (p less than 0.05) shorter than previously seen in similar studies without the infusion of a vasodilator; all animals so delivered survived 24 h of mechanical ventilation in excellent health. We suggest that pharmacologic pulmonary vasodilation, in addition to deep sustained pulmonary insufflation and distension, is an effective and rapid means of transforming stiff immature lungs into lungs that can sustain normal ventilation and gas exchange.