To determine whether exercise responses are different from normal in children with sickle cell anemia (SCA), we performed dynamic cycle ergometer exercise testing in 47 patients with SCA, aged 5 to 18 years, and 170 healthy, black age-matched control subjects. Seven (15%) of the patients with SCA had definitely ischemic, 16 (34%) had equivocally ischemic, and 24 (51%) had nonischemic ECG responses. Resting heart rate in the three groups of patients with SCA was higher than control values. Maximum exercise heart rate attained was lowest in the definitely ischemic group. All patients with SCA had decreased blood pressure responses and maximum working capacity when compared with control subjects. Hemoglobin concentration was lowest in the definitely ischemic group and correlated with maximum workload. Long-term myocardial ischemia may lead to fibrosis and the decreased myocardial contractility seen in adult patients with SCA.