The recently reported cardiac autonomic dysregulation in patients with schizophrenia is characterized by a decreased vagal and an increased sympathetic modulation. This impairment possibly contributes to the increased cardiovascular mortality rate that is up to three times higher in these patients than in general population. The aim of this study was to characterize the autonomic regulation in schizophrenia and to evidence for a genetic influence. We investigated 36 patients with schizophrenia, 36 healthy first-degree relatives and 36 healthy controls. The autonomic regulation was classified applying linear and nonlinear methods of heart rate variability analysis. Healthy relatives were compared with healthy controls matched with respect to age and gender and with patients suffering from schizophrenia. Further on, schizophrenic patients were compared with healthy controls. The results show that the autonomic regulation in healthy relatives differs significantly from healthy controls (p〈0.01) and slightly from patients. However, the most significant differences could be found between patients and healthy controls (p〈0.0001). Relatives revealed decreased heart rate variability and demonstrated an altered autonomic modulation of heart rate and similar pattern of autonomic dysfunction as patients. This autonomic impairment found in relatives might indicate an underlying disease-inherent genetic vulnerability, especially since it is known that heart rate variability is partially under genetic control.