Disturbances in autonomic control during myocardial ischemia may contribute significantly to the development of malignant cardiac arrhythmias. Therefore acute ischemia was induced in 29 mongrel dogs with healed myocardial infarctions during an exercise test. Seventeen animals developed ventricular fibrillation (susceptible, S), whereas 12 dogs did not (resistant, R). Before the exercise plus ischemia test a coronary occlusion was made at rest. The amplitude of respiratory sinus arrhythmia (0.24- to 1.04-Hz component of R-R interval fluctuation) was used as an index of cardiac vagal tone. Acute ischemia elicited a significantly larger heart rate increase in susceptible animals (S control 115.6 +/- 0.8, occlusion 176.4 +/- 8.2 beats/min vs. R control 114.6 +/- 8.9, occlusion 145.7 +/- 7.5 beats/min). Accompanying the heart rate increase were significantly greater reductions in the cardiac vagal tone index in the susceptible animals. (S control 6.4 +/- 0.3, occlusion 2.2 +/- 0.6 ln ms2 vs. R control 6.6 +/- 0.4, occlusion 5.1 +/- 0.5 ln ms2). beta-Adrenergic receptor blockade reduced the heart rate increases but exacerbated the reductions in the cardiac vagal tone index. These data suggest that coronary artery occlusion elicits a significantly greater increase in sympathetic activity coupled with a greater reduction in parasympathetic activity in animals subsequently shown to be susceptible to ventricular fibrillation.