The relative efficacy of prehepatic and central venous infusion of total parenteral nutrition (TPN) was evaluated in a chair-adapted primate model. Four adult male monkeys (Macaca fascicularis) underwent surgical placement of a silastic catheter in both the portal vein (PV) and superior vena cava (SVC). Following recovery (10 days), each animal received two courses of TPN (100 kcal and 4 g of protein/kg/day) for 10 days each via the PV and SVC in an alternating crossover manner. The prehepatic (PV) infusion of TPN in the well nourished, chair-adapted primate results in maintenance of weight (PV: delta - 0.07 kg; SVC:delta - 0.07 kg), nitrogen equilibrium (PV:+ 0.8 g N/day; SVC: + 0.7 g N/day), and trends in serum albumin (PV:delta - 0.35 g %; SVC: delta - 0.38 g %), and total iron binding capacity (PV:delta + 44 mg %; SVC:delta + 8.67 mg %) comparable to the SVC route. No significant abnormalities in liver enzyme production were observed with either route of infusion. Whole body protein synthesis rates using 15N-glycine tracer were likewise comparable (PV = 2.05 g N/kg/day; SVC = 2.18 g N/kg/day). Prehepatic delivery and primary hepatic modulation of substrates does not substantially improve the efficacy of parenteral nutrient administration. Intestinal modification of substrates may be the most important contributing factor in the supposed superiority of enteral alimentation.