Postmenopausal estrogen replacement therapy (ERT) has been associated with a reduced risk of coronary artery disease (CAD). Whether this apparent cardioprotective effect is mediated by a cardiovascular benefit during exercise, however, has not been clearly defined. To evaluate rest and exercise variables with and without ERT, a randomized crossover trial was conducted in 23 postmenopausal women, ranging in age from 44 to 75 years, mean age 57+/-8 years. The rest and exercise variables were compared on ERT and during a drug-free period. The baseline measure was compared to the effects after 4 weeks of ERT and after 4 drug-free weeks. Echocardiographic treadmill exercise variables of heart rate (HR), blood pressure, rate-pressure product (RPP), and cardiac dimensions were determined at baseline and at the end of each treatment period. In response to ERT, there was a decrease in low-density lipoprotein (LDL) cholesterol (drug-free: 142+/-40 mg/dl, ERT: 124+/-34 mg/dl) and an increase in high-density lipoprotein (HDL) cholesterol (drug-free: 52+/-14 mg/dl, ERT: 62+/-15 mg/dl, both p<0.01). At rest, the study population had no overall significant change in HR, blood pressure, RPP, or left ventricular end-systolic and end-diastolic diameters when ERT was compared to the drug-free period. However, subjects with the fastest baseline resting HR had the greatest decrease in HR with ERT relative to the drug-free period (p<0.05). During exercise, ERT effected no change in peak HR, blood pressure, or RPP, although end-systolic diameter decreased slightly (p<0.05). With ERT, subject age correlated negatively with systolic blood pressure (p<0.05) and RPP (p<0.01); both blood pressure and RPP decreased in older subjects. In conclusion, ERT has differential effects dependent on baseline HR and age.