Although both transient entrainment and resetting with single extrastimuli have been demonstrated during sustained ventricular tachycardia related to previous myocardial infarction, the relation between these phenomena has not been defined. Because transient entrainment is only demonstrated when the mechanism of a tachycardia is reentry with an excitable gap, the resetting response to timed premature extrastimuli was studied in patients with ventricular tachycardia and correlated with the ability to demonstrate transient entrainment. The importance of the location of pacing and recording electrodes relative to regions of slow conduction within the reentry circuit for demonstrating specific characteristics of the resetting response after single extrastimuli was examined in 16 patients with 21 distinct morphologies of ventricular tachycardia related to coronary artery disease. At electrophysiological study, intracardiac electrograms were recorded simultaneously from four sites in the right ventricle and four sites in the left ventricle during ventricular tachycardia. Both resetting and transient entrainment could be demonstrated for 18 of the 21 (86%) ventricular tachycardias. The resetting response at each intracardiac recording site was defined as orthodromic or antidromic, based on the conduction time from the pacing stimulus to the recording site and the morphology of the captured (advanced) electrogram. An orthodromic resetting response was associated with demonstration of transient entrainment at 76 of 82 (93%) recording sites, implying that the pacing site was proximal and the recording site was distal to a region of slow conduction. In contrast, an antidromic resetting response was associated with transient entrainment at only six of 154 (4%) recording sites, suggesting that the pacing site was not separated from the recording site by a region of slow conduction (p = 0.001). The return cycle at the site of pacing exceeded the tachycardia cycle length in all episodes of ventricular tachycardia. At orthodromically activated recording sites, however, resetting was associated with a return cycle less than the tachycardia cycle length. Thus, orthodromic resetting demonstrates that a pause is not an integral part of the resetting response but that premature extrastimuli preexcite the reentrant circuit by entering the excitable gap, conducting through a region of slow conduction, and emerging distally without a change in activation sequence. In all episodes of ventricular tachycardia, the slope of the return cycle at the pacing site was determined by the conduction properties to the orthodromically activated sites, with increasing patterns (n = 6) produced by progressive conduction delay in the reentrant circuit at shorter coupling intervals and flat patterns (n = 3) produced by a constant orthodromic conduction interval.(ABSTRACT TRUNCATED AT 400 WORDS)