We investigated whether autonomic nervous system imbalance imposed by pharmacological blockades and associated with acute myocardial infarction (AMI) is manifested as modifications of the nonlinear interactions in heart rate variability signal using a statistically based bispectrum method. The statistically based bispectrum method is an ideal approach for identifying nonlinear couplings in a system and overcomes the previous limitation of determining in an ad hoc way the presence of such interactions. Using the improved bispectrum method, we found significant nonlinear interactions in healthy young subjects, which were abolished by the administration of atropine but were still present after propranolol administration. The complete decoupling of nonlinear interactions was obtained with double pharmacological blockades. Nonlinear couplings were found to be the strongest for healthy young subjects followed by degradation with old age and a complete absence of such couplings for the old age-matched AMI subjects. Our results suggest that the presence of nonlinear couplings is largely driven by the parasympathetic nervous system regulation and that the often-reported autonomic nervous system imbalance seen in AMI subjects is manifested as the absence of nonlinear interactions between the sympathetic and parasympathetic nervous regulations. autonomic nervous system; bispectrum; heart rate variability THE NEURAL CONTROL OF the cardiovascular system exhibits complex nonlinear behavior. One form of nonlinear behavior is the continuous interaction between the sympathetic and parasympathetic nervous activities to control the spontaneous beatto-beat dynamics of heart rate. The interactions are believed to be nonlinear because physiological conditions would most likely involve autonomic nervous system regulation based on dynamic and simultaneous activity of the sympathetic and vagal responses to physical environmental stressors (1, 12, 26a). It is through efficient interactions between the sympathetic and parasympathetic nervous activities that the homeodynamic of the cardiovascular system is properly maintained. Failure of the interactions has been shown to lead to sympathetic hyperactivity, promoting the occurrence of life-threatening ventricular tachyarrhythmias, whereas augmented vagal tone exerts a protective and antifibrillatory effect (10, 26a). Experimental evidence suggests that hypertension (6), myocardial ischemia, acute myocardial infarction (AMI), sudden cardiac death, and chronic heart failure all exhibit signs of autonomic function imbalance (10). Consistent with autonomic imbalance, patients who have suffered an AMI have a marked decrease in heart rate variability (HRV), as demonstrated by an increase in sympathetic and a decrease in vagal neural activities. Thus, due to the condition of autonomic imbalance, it is possible that nonlinear interactions are a less common phenomenon in diseased states.The existence of nonlinear dynamics underlying HRV in humans has been proved by a number of previous studies (3-4...