Adrenergic mechanisms influence surfactant metabolism; however the nature and importance of catechol-mediated regulation is unclear. We designed experiments to assess the role of endogenous adrenal epinephrine (E) synthesis in neonatal alveolar surfactant release. We administered the experimental adrenal epinephrine synthesis inhibitor SKF 29661 to pregnant rabbits to reduce fetal adrenal E content. Surfactant release was measured as total alveolar phosphatidylcholine (PC) content recovered by a thorough alveolar wash performed on animals sacrificed at birth and at 1 h of age. At a maternal dose of 100 mg/kg/day, SKF 29661 caused a 57% reduction in fetal adrenal E content (p less than .01), which was associated with a 40% reduction in alveolar PC at birth and a 23% reduction in alveolar PC at 1 h of age (p less than .01). Moreover, adrenal E correlated positively with total alveolar PC content (p less than .001). These results suggest that in the neonatal period, the ability of the fetal adrenal gland to synthesize E for secretion plays a role in the regulation of pulmonary surfactant release.