The correlates of exercise left ventricular (LV) performance were examined in 45 patients with isolated mitral valve prolapse (no associated mitral regurgitation or coronary artery disease). There were 18 men and 27 women, aged 16 to 73 years; 20 patients were 40 years or younger and 25 were older than 40. The response of the LV ejection fraction (EF) to symptom-limited upright exercise was normal (at least a 5% increase) in 27 patients (60%) and abnormal in 18 (40%). There were no significant differences between patients with normal and abnormal EF response in clinical presentation, electrocardiographic findings (at rest or during exercise), medications, rest EF, heart rate (at rest or during exercise) and systemic arterial pressure (at rest and during exercise). A normal EF response was observed more frequently in patients 40 years or younger than in those older than 40 (80 vs 44%, p < 0.01), and more often in men than in women (78 vs 48%, p < 0.04). The change in EF from rest to exercise was 18 ± 9% in men and 5 ± 10% in women 40 years or younger (p < 0.01), and 9 ± 8% in men and 2 ± 8% in women older than 40 (p < 0.04). Thus, patients (especially women and those older than 40 years) with isolated mitral valve prolapse may have abnormal LV functional reserve. Genetic differences in the expression of the disease in both sexes and age-related irreversible myocardial changes may explain these observations. © 1986.