The aim of the present study was to compare the performances of gas chromatography/mass spectrometry (GC/MS) and gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) in stable isotope kinetic studies. In the analysis of cholesterol and leucine, GC/C/IRMS gave precise and linear results over a large scale of¹³C enrichment (−22 to +760 δ‰ for cholesterol, −26 to +600 δ‰ for leucine). Compared with GC/MS, GC/C/IRMS was much more accurate and reproducible, especially at low [¹³C]cholesterol enrichment (−12 δ‰), with cholesterol samples ranging from 0.11 to 17 ng. Cholesterol ester kinetics in rabbit plasma low-density lipoproteins was studied after injection of 3 mg [3,4-¹³C]cholesterol. A smooth and regular kinetic curve was obtained with GC/C/IRMS; results were much less reproducible with GC/MS. Finally, the performances of GC/C/IRMS were demonstrated in the simultaneous kinetic study of three human plasma apolipoproteins during a primed constant infusion of 0.7 mg·kg⁻¹·h⁻¹l-[1-¹³C]leucine. Kinetic curves were obtained in very-low-density lipoproteins and low-density lipoproteins for apolipoprotein B100, and in high-density lipoproteins for apolipoproteins AI and AII.