Tetrodotoxin (TTX) poisoning, although uncommon, is frequently seen in Taiwan, Japan, and Southeast Asia. It is rare but significant in the United States as well. Only three cases have been reported in the EM literature. We report an outbreak of six cases of TTX poisoning from eating puffer fish. On April 17, 2001, an outbreak of TTX poisoning occurred among Mainland Chinese fishermen who shared puffer fish on their boat in the Taiwan Strait. All six cases were middle-aged men (aged 32-49 yr). Onset of symptoms began approximately 2 to 3 hours after ingestion; symptoms included orolingual numbness, acroparesthesia, and breathlessness. As a result of delayed transportation and initial resuscitation, one patient presented in full cardiac arrest, with recovery of spontaneous circulation after successful cardiopulmonary resuscitation. With the exception of this patient, the initial acid-base abnormalities were inconsistent with severity of illness and mild hypercapnia was common (4 out of 5). The patient who presented in full arrest died 1 day after admission as a result of intractable bradycardia (complete atrioventricular block), a finding rarely mentioned in the literature, despite intravenous atropine and dopamine infusion. The remaining patients survived without significant sequelae and were discharged after short-term observation and supportive care, although some had neurologic and cardiopulmonary manifestations (muscle weakness, hypotension, hypoxemia, and hypercapnia). Some mildly hypoventilated patients recovered well without endotracheal intubation and ventilatory support. Favorable outcomes in most patients can be obtained if aggressive supportive treatment is provided in time. Thus, appropriate prehospital and ED ventilatory support (the implementation of a bag-valve mask or endotracheal intubation with good ventilatory support) is mandatory for those patients with respiratory failure. Most patients experience onset of symptoms within 6 hours of ingestion, but a few have a delayed onset up to 20 hours. Therefore, for those TTX-intoxicated patients without immediate prominent respiratory insufficiency, at least 24 hours of intensive monitoring of their respiratory state is necessary because of the different susceptibility and unpredictability of an individual course.