It is not known whether female hormonal replacement therapy (HRT) influences fasting plasma lipoprotein lipids in diet-treated hypercholesterolemic subjects. Thirteen moderately hypercholesterolemic postmenopausal women were studied during dietary treatment alone with a low fat, low cholesterol diet for the 3 months and during the subsequent 2 y of HRT with dl-norgestrel (0.075 mg daily) and estradiol-17 beta (1 mg, 25 of 28 days) with maintenance of the same diet. Hormonal replacement therapy decreased plasma total cholesterol by 11 +/- 3% (5.7 vs. 6.4 mmol/L, p < 0.005), due to a 17 +/- 3% mean reduction (p < 0.001) in the concentration of plasma low density lipoprotein cholesterol (3.9 vs. 4.7 mmol/L, p < 0.001). The ratio of plasma total cholesterol to high density lipoprotein cholesterol fell significantly by 17 +/- 4% (4.1 vs. 4.9, p < 0.005). Mean fasting plasma concentrations of total triglycerides (1.1 vs. 1.6 mmol/L, p < 0.005) fell by 31 +/- 6%, and very low density lipoprotein triglycerides (0.56 vs. 0.83 mmol/L, p < 0.02) by 33 +/- 9%. Hormonal replacement therapy was well-tolerated, improved mood levels, and increased the mineral content of the vertebral spine significantly, while effectively relieving vasomotor flushing. Hormonal replacement therapy complements the dietary treatment of hypercholesterolemia.