Directed surgical intervention in patients with ventricular tachyarrhythmias who have experienced failure of amiodarone therapy is a common clinical scenario. Sixty-seven patients with malignant ventricular tachyarrhythmias received either an automatic implantable cardioverter-defibrillator (n = 43) or subendocardial resection (n = 24). Nineteen cardiothoracic procedures (automatic implantable cardioverter-defibrillator in six, endocardial resection in 13) were performed in 17 patients who received amiodarone before surgery. Eight received the drug acutely as a loading dose of 1,200 mg/day for 7-14 days; 11 patients were on chronic oral amiodarone at a mean dose of 362 +/- 74 mg/day. Eight patients were removed from amiodarone therapy a mean of 6.6 days before surgery. Adult respiratory distress syndrome (ARDS) developed after surgery in nine (50%) of 18 surgical survivors. ARDS was manifested by hypoxemia, pulmonary infiltrates, and prolonged intubation. Pulmonary capillary wedge pressure and cardiac output were measured before and after surgery and during ARDS. Pulmonary capillary wedge pressure and cardiac output remained constant after surgery at a time that the PaO2/FIO2 ratio fell significantly. By contrast, none of the remaining 44 patients who did not receive amiodarone developed ARDS despite similar preoperative and intraoperative clinical parameters. Patients with ventricular tachyarrhythmias who receive even a short course of amiodarone are at risk for postoperative ARDS.