To evaluate the role of splanchnic and renal tissues in epinephrine disposal, we infused epinephrine (60 ng X kg-1 X min-1) into nine human volunteers during hepatic (n = 6) and/or renal (n = 4) vein catheterization. During the infusion plasma epinephrine rose higher in the artery (1,345 +/- 126 pg/ml) than in the hepatic (218 +/- 42 pg/ml) or renal vein (528 +/- 95 pg/ml). Splanchnic plasma flow increased by 43% (P less than 0.001), whereas renal plasma flow was unchanged. Net epinephrine uptake increased to a greater extent (3-fold) in the splanchnic area as compared with the kidney, amounting to 32 +/- 3% and 10 +/- 2% of the infused epinephrine load, respectively. The splanchnic epinephrine clearance also increased by 50-60%, while fractional extraction remained stable at 80-85%. Renal epinephrine clearance and extraction was not significantly altered, however. Epinephrine infusion caused splanchnic norepinephrine uptake to increase as well, partially because of the increased plasma flow. In contrast, the kidney showed net norepinephrine production throughout. We conclude that the splanchnic area plays a much more important role than the kidney in the disposal of circulating epinephrine. The great efficiency of splanchnic epinephrine removal is further enhanced by epinephrine-induced hemodynamic changes that also promote the splanchnic uptake of norepinephrine.