Extracellular and intracellular longitudinal resistances (r0and r1), transmembrane potentials, and conduction velocity were determined in arterially blood-perfused rabbit papillary muscles. Cable analysis was made possible by placing the muscle in a H2O-saturated gaseous environment, which acted as an electrical insulator. Ischemia was produced by exchanging the O2in the atmosphere by N2(94% N2-6% CO2) in addition to arresting coronary flow. The first 10–15 minutes of ischemia were characterized by an increase in r0, while r1remained constant. The early part of the increase in r0coincided with the drop in perfusion pressure and was probably due to the diminution of intravascular volume. Rapid electrical uncoupling, reflected by an increase in r1(threefold within 5 minutes), occurred thereafter. The dissociation between the early increase in r0and the delayed increase in r, produced an initial increase in the ratio r0:r1, which subsequently decreased. The decrease in conduction velocity was less than observed in intact hearts with ischemia. This difference is explained by the relatively small changes in resting membrane potential and action potential amplitude in the preparation used. Our results suggest that in the early, reversible phase of ischemia, the increase in r0contributes to a small but significant extent to the slowing of conduction. After 15–20 minutes, the rapid cellular uncoupling, which was most likely coincident with breakdown of cellular homeostasis, may contribute to the occurrence of arrhythmias during this phase of ischemia. Moreover, the early change in the ratio r0: r1will influence the amplitude of the extracellular electrograms following coronary occlusion (TQ-segment and ST-segment shifts).