The bed nucleus of the stria terminalis (BNST) is involved in autonomic and behavioral reactions to fearful stimuli and contains corticotropin-releasing hormone (CRH) fibers and terminals. The role of CRH in the medial part of the BNST in the regulation of heart rate (HR) and PQ interval of the electrocardiogram was studied under resting conditions and conditioned fear stress in freely moving rats. Microinfusion of CRH (0.2 microg/0.6 microl) in the medial BNST under resting conditions significantly enhanced HR as compared to saline treatment, but did not reduce the PQ interval, indicating that exogenous CRH in the medial BNST can activate both the sympathetic and parasympathetic cardiac outflow. In addition, CRH induced a slight increase in gross locomotor activity, an effect that succeeded the tachycardiac response, indicating that the HR response was not a consequence of increased locomotor activity, but likely a direct effect of CRH. CF was induced by 10-min forced exposure to a cage in which the rat had experienced footshocks (5 x 0.5 mA x 3s) the day before. alpha-helical CRH(9-41) (alphahCRH; 5 microg/0.6 microl), a non-selective CRH receptor antagonist, or saline was infused into the medial BNST of rats prior to CF. CF induced freezing behavior, associated with an increase in HR and PQ interval, indicating activation of sympathetic and vagal outflow to the heart. alphahCRH significantly reduced the PQ response, but enhanced the tachycardia, suggesting inhibition of vagal activity. In addition, alpha-helical CRH(9-41) reduced the freezing response. Taken together, the data provide first evidence that CRH, released in the medial BNST during stress, contributes to cardiac stress responses, particularly by activating vagal outflow.