The haemodynamic responses to isometric exercise of eight recipients of orthotopic heart transplants and eight healthy controls were studied. Each performed sustained exercise at 30% of maximal voluntary contraction for three minutes on a handgrip dynamometer. Cardiac output was measured by combined Doppler and cross sectional echocardiography before exercise and every 30 seconds during and after exercise. In the controls cardiac output and blood pressure increased significantly owing to an increase in heart rate with no change in stroke volume. In the transplant group cardiac output, heart rate, and stroke volume remained unchanged throughout exercise. In contrast with its response to dynamic exercise the denervated human heart is unable to increase cardiac output during isometric exercise. The pressor response that occurs is mediated via an increase in peripheral vascular resistance.