This study examined the short-term effects of three total parenteral nutrition solutions, each containing a different lipid source, on host and tumor protein metabolism in a rat cancer model. Each diet contained 220 kcal/kg per day, including 2 g of nitrogen/kg per day and 50% of nonprotein calories as either a structured lipid of medium-chain triglycerides and fish oil, a physical mix of medium-chain triglycerides and fish oil, or Liposyn II, a long-chain triglyceride. A 3-day intravenous feeding infusion began on day 7 after tumor implantation. Tumor growth rate, nitrogen balance, energy expenditure, and plasma albumin, glucose, and free fatty acids were measured, and whole body protein kinetics and fractional synthetic rates in liver, muscle, and tumor tissues were assessed using a constant infusion of 14C-leucine. The results revealed that tumor growth rate was slowed in structured lipid-fed animals (p = .06, one-way analysis of variance) with significant increases in rates of tumor protein synthesis and tumor protein breakdown (p < .001, one-way analysis of variance). Although muscle fractional synthetic rates were significantly decreased in tumor-bearing animals (p < .05, two-way analysis of variance), the rates in structured lipid-fed animals were restored. Nitrogen balance improved significantly in structured lipid-fed animals. The results demonstrate that the source of lipid in total parenteral nutrition solutions can influence tumor and host protein metabolism, and that a structured lipid composed of medium-chain triglycerides and fish oil seems to improve protein metabolism in host tissue without stimulating tumor growth.