Oestradiol-17 beta causes relaxation of isolated coronary arteries and increases blood flow in several vascular beds in human beings and animals. Oestrogen replacement therapy is associated with a lower incidence of cardiovascular disease, but the acute effects of oestradiol-17 beta on myocardial ischaemia are unknown. We have studied the acute effect of sublingual oestradiol-17 beta on exercise-induced myocardial ischaemia in eleven women (mean age 58 [SD 8] years) with coronary artery disease. The women did two treadmill exercise tests on separate days; 40 min before the test they took sublingual oestradiol-17 beta (1 mg) or placebo, in random order. Plasma oestradiol-17 beta concentrations were confirmed to be higher after sublingual oestradiol-17 beta than after placebo (2531  vs 155  pmol/L, p < 0.001). Oestradiol-17 beta increased both time to 1 mm ST depression (456  vs 579  s, p < 0.004; difference of medians 92 [95% CI 46-254]) and total exercise time (569  vs 658  s, p < 0.01; difference 54 [10-212]). Acute administration of oestradiol-17 beta therefore has a beneficial effect on myocardial ischaemia in women with coronary artery disease. This effect may be due to a direct coronary-relaxing effect, to peripheral vasodilation, or to a combination of these mechanisms. Oestradiol-17 beta may prove to be a useful adjunct to the treatment of angina in postmenopausal women with coronary heart disease.