Hyperlipidemia occurs in animals bearing tumors but the mechanism of its development is uncertain. We have measured triacylglycerol clearance and production rate in rats bearing a transplantable sarcoma. The plasma content of very-low-density lipoprotein triacylglycerol was increased in these tumor-bearing rats but our data excluded a primary clearance defect because the rate of triacylglycerol accumulation (mg/min) after Triton injection was equal to or greater than in normal control rats, except in cachectic rats with very large tumors. The fractional clearance of injected radioactive triacylglycerols was less in tumor-bearing rats than in controls, but the turnover (mg/min) was probably not decreased in the tumor-bearing rats because of their expanded plasma pool. Also inconsistent with a decreased turnover was our finding of a greater production of radioactive plasma triacylglycerols after injection of a tracer dose of radioactive free fatty acid, and unchanged production in Triton-treated rats. Therefore, in the fasted state, the hyperlipidemia of the tumor-bearing rats was associated with an unchanged or possibly an increased flux of hepatic triacylglycerols and a primary clearance defect was excluded. After fat-feeding, rats with tumors developed a higher post-prandial hyperlipidemia than control rats. Therefore, the clearance mechanism for the plasma triacylglycerols was close to saturation in the fasted state, and the added influx of exogenous triacylglycerols was removed less efficiently in the tumor-bearing rats.