The effects on lipoprotein metabolism of female hormone replacement therapy (HRT) for 7 weeks with combined low dosages of a widely used oral progestin and estrogen combination, medroxyprogesterone acetate ([MPA] 2.5 mg/d) and conjugated equine estrogen ([CEE] 0.625 mg/d), were studied in six postmenopausal women. To investigate the mechanism of the reduction of low-density lipoprotein (LDL) cholesterol by HRT, the kinetics of very-low-density lipoprotein (VLDL) and LDL apolipoprotein (apo) B turnover were studied by injection of autologous 131I-labeled VLDL and 125I-labeled under control conditions and again in the fourth week of HRT. HRT induced (1) a 12% +/- 4% (P < .02) reduction of the cholesterol content of LDL of Sf 0-12, which was attributable to a 15% +/- 5% decrease in the mean ratio of cholesterol to apo B (1.3 +/- 0.1 v 1.5 +/- 0.1, P < .025), and (2) a 13% +/- 4% increase in the mean fractional catabolic rate (FCR) of LDL apo B (0.34 +/- 0.03 v 0.30 +/- 0.02 pools/d, respectively, P +/- .05). However, there were no significant changes in mean values for (1) pool size (42 +/- 4 v 43 +/- 3 mg/kg) or production rate (14 +/- 0.5 v 13 +/- 0.9 mg/kg/d, P > .1) of LDL apo B or (2) pool size (2.5 +/- 0.6 v 2.8 +/- 0.6 mg/kg), FCR (8.0 +/- 2.0 v 8.1 +/- 1.7 pools/d) or production rate (16 +/- 4 v 19 +/- 2 mg/kg/d, P > .4) [corrected] of VLDL apo B. HRT increased high-density lipoprotein (HDL) cholesterol concentration significantly (by 16% to 18%, P < .05), whereas the mean ratio of plasma total cholesterol to HDL cholesterol decreased by 19% +/- 3% (P < .005). HRT favorably influenced the overall plasma lipoprotein lipid vascular risk profile while significantly altering both the composition and fractional catabolism of LDL.