Mechanical ventilator support and the resumption of spontaneous ventilation or weaning create significant alterations in alveolar and intrathoracic pressure that influence thoracic blood volume and flow. Compensatory autonomic tone alterations occur to ensure adequate tissue oxygen delivery, but autonomic responses may produce cardiovascular dysfunction with subsequent weaning failure. The authors describe autonomic responses of critically ill patients (n = 43) during a 24-hr period of mechanical ventilatory support and during the 24 hr that included their initial spontaneous breathing trial using continuous positive airway pressure. Nearly two thirds of these patients demonstrated abnormal autonomic function and this dysfunction was more severe in those patients who were unable to sustain spontaneous ventilation (n = 15). With further systematic study, autonomic responses may be useful in the identification of patients who are likely to develop cardiac dysfunction with the resumption of spontaneous breathing.