Circulatory collapse and sudden death was defined retrospectively as one of the major critical problems among 23 respirator-dependent patients with amyotrophic lateral sclerosis (ALS). Six cases died from sudden cardiac arrest or anoxic encephalopathy following the circulatory collapse. In five among the six cases, sudden death or cardiac arrest occurred during sleep at night. Eight cases had had episodes of marked fluctuation of blood pressure before death, including paroxysmal elevation of blood pressure and heart rate, and successive sudden pressure fall without compensatory tachycardia. The spells of hypotension often occurred during sleep. In addition, the prospective study of diurnal variation of blood pressure, heart rate, plasma norepinephrine and plasma renin activity in nine respirator-dependent ALS patients showed continuous tachycardia and more remarkable nocturnal decrease of blood pressure compared with the control subjects. Plasma norepinephrine levels were constantly higher in the ALS patients particularly in a daytime. These indicate the continuous sympathetic hyperactivity in ALS. We discuss the cause of the circulatory collapse and sudden death in the respirator-dependent ALS patients in terms of the autonomic dysregulatory mechanism or the sympathetic hyperactivity.