This study examines the recently reported gender differences in cardiac responses to exercise. The study group consisted of 192 men and 67 women with a low probability of coronary artery disease who underwent supine exercise radionuclide angiography. Men had a lower rest ejection fraction than that of women (0.63 versus 0.66, p = 0.02) and greater increases in ejection fraction with exercise (0.08 versus 0.02, p = 0.0001). The slope relating ejection fraction to metabolic equivalents of exercise (METs) was greater (p = 0.004) for men, even after adjustment for differences in rest ejection fraction and end-diastolic volume index. Compared with men, women had a smaller rest end-diastolic volume index (87 versus 97 ml/m2, p = 0.003) and a greater increase in end-diastolic volume index with exercise (6 versus -2 ml/m2, p = 0.002). The slope relating end-diastolic volume to METs was greater for women, even after adjustment for differences in rest end-diastolic volume index and peak work load. There are clear gender differences in the supine exercise response of ejection fraction and end-diastolic volume that are not explained by differences in exercise capacity.