Using an isolated salt-perfused lung model in rabbits from 1 to 21 d of age, we measured the concentration of epinephrine in the pulmonary venous drainage and the pulmonary vascular response after a single dose of intratracheal epinephrine (0.1 microgram/g body weight). Lungs from 30 rabbits were isolated, ventilated, and perfused at one of four age groups (n = 7-8 per group). After ventilation/perfusion was judged to be stable, saline control was injected into the trachea, changes in pulmonary pressure were recorded, and perfusate was collected for 45 s. After restabilization, epinephrine was injected into the trachea, changes in pulmonary vascular pressure were recorded, and perfusate was collected for 45 s x two aliquots. Perfusate epinephrine concentrations were determined by HPLC. Little epinephrine was detected in the perfusate after control over all age groups, and little vascular response was noted. There was a significant age-related increase in perfusate epinephrine concentration as well as an age-related increase in vascular response (increased PAP), with the maximum epinephrine concentration and change in PAP noted at 14-21 d [group 4 = (1.72 +/- 0.42) x 10(4) pmol/L]. Also, in rabbits less than 6 d of age, deposition of epinephrine into the pulmonary venous drainage was delayed. In the rabbit model, the concentration of epinephrine reaching the heart via pulmonary circulation after intratracheal injection is, at birth, very low, and the pulmonary vascular response is diminished. Both increase as a function of age until 14-21 d of age. These findings may have clinical importance in human neonatal resuscitation endeavors.