Anodal excitation may contribute to the initiation of ventricular arrhythmias during bipolar pacing in the canine ventricle. To determine if anodal excitation occurs during bipolar programmed ventricular stimulation in humans, ventricular electrograms adjacent to the anode and cathode were recorded using a specially designed hexapolar electrode catheter in 10 patients. Single extrastimuli were delivered during ventricular pacing at stimulus strengths slightly above the late diastolic threshold and at 2 to 5 times late diastolic threshold. Evidence of anodal excitation was observed in 18 of the 52 combinations (35%) of stimulus strengths and electrode configurations tested, and occurred in 9 of the 10 patients; it consisted of earliest ventricular activation adjacent to the anode (8 patients) or simultaneous activation at the anode and cathode (3 patients). This occurred either with premature stimuli (3 patients) or during the basic drive and extrastimuli (6 patients). Comparison of local activation times during unipolar pacing supported an anodal contribution to excitation during bipolar pacing and suggested that inhomogenous conduction delays were not responsible for these findings. Thus, anodal excitation occurs frequently during bipolar programmed stimulation and produces marked changes in local myocardial activation, which may potentially influence the initiation of ventricular arrhythmias.