Twenty-four hour noninvasive ambulatory blood pressure and heart rate monitoring was performed on patients who underwent orthotopic cardiac transplantation, as part of the investigation of the de novo hypertension that developes in such patients. Patients with essential hypertension served as control subjects. The results demonstrated a highly significant loss of the usual decline in blood pressure and heart rate during sleep in the transplant patients. A similar loss of nocturnal decline in blood pressure was noted in a group of 10 patients with autonomic neuropathy secondary to diabetes mellitus. The de novo hypertension associated with cardiac transplantation is probably multicausal. Impairment of renal function by cyclosporin-A with associated salt and water retention and persistent elevation of the systemic vascular resistance in the presence of a restored normal cardiac output by the “new” heart are major factors. In addition, loss of the normal nocturnal decline in blood pressure and heart rate, which probably is related to the denervated state of the transplanted heart, may play an important role in blood pressure control.