To determine if electrical stimulation during the basic ventricular drive train introduces local effects that influence ventricular refractoriness during endocardial stimulation in humans, 10 patients were studied. With a hexapolar catheter with 3 mm interelectrode distances positioned at the right ventricular apex, the ventricular functional and effective refractory periods were determined for unipolar cathodal stimuli of 2 and 5 times diastolic threshold. Stimulation was performed with both the scanning extrastimulus (S2) and basic ventricular drive stimuli (S1) delivered to the same site and to sites separated by 6 mm. The functional refractory period was not changed by delivering the basic drive and extrastimuli to the same as opposed to separate sites (273.5 +/- 16 vs 273.5 +/- 19 msec during stimulation at 2 times threshold and 270 +/- 16 vs 270 +/- 18 msec at 5 times threshold; p = NS). The longest S1-S2 interval at which S2 failed to capture (effective refractory period) was longer by 5.5 +/- 8.2 msec at twice threshold (0.05 less than p less than 0.10) and 5.5 +/- 3.5 msec at 5 times threshold stimulation (p less than 0.01) when the basic drive and extrastimuli were delivered to separate sites. This is consistent with later activation of the extrastimulus sites during the basic drive when the stimulation sites were separate. Thus, with this method of endocardial programmed electrical stimulation, separation of the stimulation sites for the basic drive and extrastimuli does not affect ventricular refractoriness determined by the extrastimulus technique.