We tested the hypothesis that peripheral afferent nerve stimulation decreases the incidence of ventricular arrhythmias induced by central nervous system stimulation. The hypothalamus in each of 24 anesthetized rabbits (12 with anterior myocardial ischemia) was electrically stimulated for 10 s with 10-min intervals between each of six consecutive stimulation episodes. The left peroneal nerves were electrically stimulated for 15 min beginning 5 min after the second hypothalamic stimulation episode in six ischemic and six nonischemic rabbits. Cardiac rhythm was monitored with the electrocardiogram lead I and atrial and ventricular electrograms. Hypothalamic stimulation alone induced ventricular arrhythmias [mean no. of arrhythmic beats occurring during 3rd and 4th hypothalamic stimulation episodes: nonischemic animals, 20 ± 8; ischemic animals, 62 ± 41 (P < 0.05 by unpaired t-test)]. Peroneal nerve stimulation reduced the number of arrhythmic beats induced by hypothalamic stimulation in nonischemic animals (6 ± 5; P < 0.05 vs. without peroneal stimulation) and prevented an increase in arrhythmic beats during ischemia (21 ± 16). Thus peripheral nerve stimulation decreased the number of ventricular arrhythmic beats induced by repeated hypothalamic stimulation in both ischemic and normal rabbit hearts and may be important in the prevention of arrhythmias in patients.