Although endurance exercise and supplemental estrogen have both been shown to improve serum lipid cardiac risk profiles in postmenopausal women, data regarding a possible synergistic influence are scarce and inconsistent. The purpose of this study was to determine whether such a synergistic influence could be demonstrated. Serum concentrations of total cholesterol (TC), HDL-cholesterol (HDL-C), HDL2-C, HDL3-C, LDL-C, and triglycerides (TG) were obtained from postmenopausal women (N = 45) in each of 4 groups: currently exercising and taking estrogen replacement, exercising and not taking estrogen, sedentary and taking estrogen, and sedentary and not taking estrogen. HDL-C was on average 21% higher (p < .05) and the HDL-C:LDL-C ratio on average 45% higher (p < .05) in the exercise-plus-estrogen group than in any of the other 3 groups. It was concluded that the combination of endurance exercise and estrogen replacement might be associated with better lipid coronary risk profiles in postmenopausal women than either intervention alone.