To characterize pulmonary and total body norepinephrine and epinephrine kinetics in the immediate newborn period, the effects of desipramine were studied in six fetal lambs chronically instrumented at 133-134 days gestation (term 147 days) and delivered 1 wk later by cesarean section under spinal anesthesia. Norepinephrine and epinephrine kinetics were determined with isotope dilution methodology 4 h after birth and repeated 30 min after desipramine (2 mg/kg iv). At baseline, the lungs accounted for 35 ± 10 and 47 ± 13% of whole body norepinephrine clearance (93 ± 8 ml · min¹ · kg¹) and spillover (188 ± 29 ng · min¹ · kg¹) and 15 ± 2 and 19 ± 7% of whole body epinephrine clearance (82 ± 4 ml · min ¹ · kg ¹) and release (22.7 ± 2.7 ng · min¹ · kg¹), respectively. Desipramine decreased pulmonary norepinephrine and epinephrine clearance and spillover to near-zero levels, whereas whole body norepinephrine clearance fell by 51 ± 3% (P < 0.001), norepinephrine spillover by 54 ± 6% (P < 0.005), epinephrine clearance by 30 ± 6% (P < 0.01), and epinephrine spillover by 34 ± 11% (P < 0.05). These results indicate that, in the immediate newborn period, pulmonary removal and release of norepinephrine and epinephrine is mediated by a desipramine-sensitive process that accounts for a major portion of associated reductions in whole body norepinephrine and epinephrine clearance and release.