We compared the specificity of exercise electrocardiography in 1880 men and 1818 women with women grouped by menopausal and estrogen replacement status. Specificity far greater than or equal to 1 mm horizontal or downsloping ST-segment depression was determined using angiography in 781 patients and using two other nonangiography-based methods (a pretest probability-based method and a predictive accuracy-based method) in all patients. Using angiography, the specificities+/-SE were 84+/-2 for men, 79+/-3 for women, 81+/-5 for premenopausal women, 81+/-4 for postmenopausal women without estrogen replacement, and 77+/-5 for women on estrogen replacement. None of these were significantly different. For all patients, the respective specificities using the probability and predictive accuracy-based methods were 97+/-1 and 94+/-1 for men, 90+/-1 and 88+/-1 for women, 97+/-1 and 92+/-2 for premenopausal women, 92+/-4 and 88+/-3 for postmenopausal women without estrogen replacement, and 85+/-4 and 81+/-3 for women on estrogen replacement. (Men vs. all women groups except premenopausal women -- P<0.05). Therefore, the premenopausal women had significantly greater specificity than women on estrogen replacement (P<0.001) and no difference in specificity with men. Women on estrogen replacement had a significantly lower specificity than postmenopausal women not on estrogen replacement (P<0.05). These results suggest that estrogen replacement therapy and not naturally occurring estrogen has a role in producing false positive exercise electrocardiograms in women. (C) 1997 Elsevier Science Ireland Ltd.