OBJECTIVE We sought to assess the hemodynamics of exercise in patients with hypertrophic cardiomyopathy (HCM), with and without an exercise-induced abnormal blood pressure (BP) response, by ambulatory radionuclide monitoring of left ventricular (LV) function with the VEST device (Capintec Inc., Ramsey, New Jersey). BACKGROUND Blood pressure fails to increase >20 mm Hg during exercise in about one-third of patients with HCM. This carries a high risk of sudden death. METHODS Forty-three patients with HCM and 14 control subjects underwent maximal symptom-limited exercise on a treadmill during VEST. The VEST data were averaged for 1 min and analyzed at baseline, 3 min and peak exercise. The LV end-diastolic, end-systolic and stroke volumes, cardiac output and systemic vascular resistance were expressed as the percentage of baseline. RESULTS Ejection fraction and stroke volume fell in patients with HCM, although they increased in control subjects (p < 0.001 and p = 0.002, respectively). Cardiac output increased significantly more in control subjects than in patients with HCM (p = 0.001). In 17 patients with HCM (39%) with an abnormal BP response, ejection fraction and stroke volume fell more (p = 0.032 and p = 0.009, respectively) and cardiac output increased less (p = 0.001) than they did in patients with HCM with a normal BP response. Systemic vascular resistance decreased similarly in patients with HCM, irrespective of the BP response. CONCLUSIONS In patients with HCM with and without an abnormal BP response, abnormal hemodynamic adaptation to exercise was qualitatively similar but quantitatively different. An abnormal BP response was associated with exercise-induced LV systolic dysfunction. This causes hemodynamic instability, associated with a high risk of sudden cardiac death.