This study assesses the impact of permanent dual chamber (DDD) pacing on symptoms and rest and exercise hemodynamics in patients with hypertrophic cardiomyopathy and no resting left ventricular outflow gradient, significantly symptomatic despite attempts at medical management. Following baseline echocardiography, treadmill exercise testing, thallium-201 scintigraphy, radionuclide angiography and invasive measurement of rest in semi-erect bicycle exercise hemodynamics, 20 consecutive patients with hypertrophic cardiomyopathy and no resting left ventricular outflow gradient underwent implantation of a DDD pacemaker. Patients then returned approximately 4 months later for a repeat of these studies to assess the impact of permanent DDD pacing on symptoms and hemodynamic indices. One patient died 3 months following pacemaker implantation because of worsening diastolic heart failure. However, of the remaining 19 patients, 16 improved in symptoms by at least one New York Heart Association Functional Class. There was no change in rest or exercise left ventricular ejection fraction or cardiac dimensions during DDD pacing compared to the baseline studies in sinus rhythm. Treadmill exercise duration was longer by over a minute during DDD pacing compared to the baseline study in sinus rhythm. However, there was a small but significant reduction in the stroke volume index at rest and submaximal exercise. There were no significant differences in any other hemodynamic indices at rest or during exercise with DDD pacing compared to the baseline exercise studies in sinus rhythm. Because of significantly worsened effort tolerance during DDD pacing compared to baseline in 2 patients, pacemakers were programmed to back up VVI mode. Thus, DDD pacing in patients with hypertrophic cardiomyopathy and no resting obstruction was associated with improvement in symptoms and effort tolerance in many patients but without net change in exercise hemodynamics, and evidence for worsened effort tolerance and exercise hemodynamics in some patients. Benefit from chronic pacing may be compromised in some patients by reduction in rest and exercise stroke volume.