There is evidence that serotonin (5-hydroxytryptamine) may be released from pulmonary neuroendocrine cells during hypoxia in animals. Because there are few data regarding serotonin's effect on the immature pulmonary circulation, we studied the direct pulmonary (and systemic) vascular effects of this amine in awake lambs. As has been observed in mature animals, we found that serotonin is a powerful pulmonary and systemic vasoconstrictor, with a threshold of 3 μg/kg in immature lambs. However, unlike in mature animals, phenoxybenzamine, 2 mg/kg, prevented both the pulmonary (and systemic) vasoconstriction seen with serotonin. Serotonin is a powerful pulmonary vasoconstrictor in immature lambs, which is consistent with the idea that release of serotonin from pulmonary neuroendocrine cells may play a role in the hypoxic pulmonary vasoconstrictor response.