Background-The purpose of this study was to compare differential effects of a segment of slow conduction during ventricular tachycardia (VT) due to depression of the action potential and electrical uncoupling. Methods and Results-In 33 Langendorff-perfused rabbit hearts, a ring of anisotropic left ventricular subepicardium was created by a cryoprocedure. Reentrant VT was produced by incremental pacing. Slow conduction in a segment of the ring was created by selective perfusion of the LAD with 10 mmol/L potassium or 0.75 mmol/L heptanol. As a result, VT cycle length increased from 193Ϯ34 to 235Ϯ37 ms (potassium) and 227Ϯ42 ms (heptanol). Reset curves were made by applying premature stimuli proximal to the area of depressed conduction. In a ring of uniform anisotropic tissue, the reset curve was almost completely flat. Electrical uncoupling of part of the ring (nonuniform anisotropy) resulted in a mixed reset curve. In both substrates, early premature beats failed to terminate VT. Depression of part of the ring by increasing K ϩ resulted in a completely sloped reset curve, indicating a gap of partial excitability. Under these conditions, in 19 of 24 hearts, premature beats terminated VT by conduction block in the high K ϩ area. Conclusions-The nature of the area of slow conduction determines the type of reset response and the ability to terminate VT. (Circulation. 1999;99:949-962.)