The hypothesis of this study was that changes in arterial determinants of afterload due to static muscular contraction can be modified, in postmenopausal women, by estrogen replacement therapy. Two groups of 14 postmenopausal and 15 premenopausal women were enrolled. Hemodynamic changes induced by right handgrip were recorded between days 7 and 10 of the menstrual cycle in premenopausal women. The same recordings were performed in postmenopausal women, before and after receiving transdermal estrogen replacement therapy for 8 days. Handgrip was performed at 50% of maximal voluntary contraction and maintained until exhaustion. Arterial pressure and blood velocity were recorded in the resting hand with photoplethysmographic and Doppler techniques. Indices of arterial elasticity and resistance were calculated. In postmenopausal women, these indices increased during effort only slightly less after therapy than before, if the mean values and statistical significance were considered, but the most evident effect of therapy was a decrease in interindividual differences in the effort induced changes. This means that, after therapy, increases in arterial resistance and elasticity indices were appreciably prevented mainly in those postmenopausal women who, before therapy, showed the greatest increases. Differences due to therapy were negligible in postmenopausal women in whom, before estrogen replacement, increases in elasticity and resistance indices during effort were similar to those obtained in premenopausal women. After therapy, no differences were found in resting conditions in any of the investigated cardiovascular parameters. Estrogen replacement did not appreciably affect changes in some arterial afterload-related indexes during handgrip, if the average values were considered in a group of postmenopausal women, but uneven and unpredictable peaks in individual responses were cut off, with a better predictability of the responses to sustained muscular contractions, as well as of the related risk factors.