A 20-second bolus of serotonin (5-hydroxytryptamine, 5HT), prostaglandin E1 (PGE1·) or norepinephrine (NE) was infused into the pulmonary arteries of lungs isolated from 26-day gestation fetal, newborn (within 12 h of birth), and young adult rabbits. In each case the concentration of the infused substrate was much less than the apparent Michaelis constant for the uptake process. At these low concentrations there was no observable vasoactivity. In order to assure a constant ratio of flow to capillary surface area (independent of lung size), perfusate flow was adjusted so that the retention time of a vascular dye was approximately 7 s. Under these conditions the isolated adult rabbit lungs inactivate a similar fraction (40–50%) of each of the substrates. In contrast, isolated newborn rabbit lungs inactivate about 20% of the infused PGE1, 90% of the 5HT, and 60% of the NE, and the nonventilated, previable fetal rabbit lungs inactivate about 20% of the infused PGE1 60% of the 5HT, and 80% of the NE.