The response of the systemic, pulmonary, hepatic and portal circulations to infusion of dopamine and epinephrine was studied in newborn piglets 1 to 3 d of age. Anesthetized animals were instrumented to measure cardiac index (CI), hepatic arterial flow, and portal venous blood flow. Catheters were inserted for measurement of systemic arterial pressure (SAP), pulmonary arterial pressure (PAP), and for sampling of arterial, portal venous, and mixed venous oxygen saturations and plasma lactate levels. Systemic, pulmonary and mesenteric vascular resistance indices (SVRI, PVRI, MVRI), and systemic and mesenteric oxygen extraction were calculated. Dopamine and epinephrine were infused in doses of 2, 10, 32 microg/kg/min and 0.2, 1.0, 3.2 microg/kg/min respectively, given in random order. Significant increases in SAP, PAP, and CI were demonstrated with 32 microg/kg/min of dopamine and the two higher doses (1.0 and 3.2 microg/kg/min) of epinephrine. There were no significant changes in SVRI and PVRI with dopamine infusions. Epinephrine at 3.2 microg/kg/min significantly elevated SVRI and PVRI. The SAP/PAP ratio was decreased with 32 microg/kg/min of dopamine whereas epinephrine did not affect the ratio. Dopamine had no significant effect on hepatic arterial flow, portal venous flow, or mesenteric vascular resistance. Epinephrine infusion at 3.2 microg/kg/min decreased portal venous blood flow, total hepatic blood flow, and hepatic oxygen delivery with an increase in calculated mesenteric vascular resistance. Systemic and mesenteric oxygen extraction were not affected by dopamine or epinephrine infusions. Plasma lactate levels were significantly elevated with epinephrine infusion 3.2 microg/kg/min. The differential responses of dopamine and epinephrine on pulmonary and mesenteric circulations may be significant in the pathophysiology and management of persistent fetal circulation and necrotizing enterocolitis.