Stable isotope methodology has been adapted to the study of lipoprotein turnover in human subjects. Using endogenous [15N]glycine labeling and gas-liquid chromatographic-mass spectrometric analysis, synthesis of apolipoprotein B in very low density lipoprotein (VLDL) was measured directly in five normal and two hyperlipidemic subjects. An isotopic precursor steady state was achieved during the studies by utilizing a priming dose and constant infusion containing [15N]glycine. Measurement of the plateau in 15N enrichment in the urinary hippurate produced during each study was used to estimate the 15N enrichment of the hepatic glycine precursor pool. The range of values for the fractional synthetic rate of VLDL apoB in the normal subjects obtained by this method was 5.9 to 11.5 day-1, with a mean of 9.2 +/- 2.4 (SD). This value agrees with the results of previous investigations which have utilized other methods. The method was also tested in two hypertriglyceridemic subjects and gave fractional synthetic rates of VLDL apoB that were significantly lower than in normals (1.5 and 2.8 day-1). This stable isotope method allows calculation of the fractional synthetic rate of VLDL apoB by maintaining an isotopic steady state throughout the study. It makes possible repeated studies in the same individual since no risk of exposure to radioisotopes is involved.