Conduction velocities along longitudinal (vL) and transverse (VT) fiber axes were determined in isolated porcine hearts from subepicardial activation patterns that were produced by local stimulation and measured with a multiterminal electrode. In some of the experiments extracellular [K'] ([K'].) and transmembrane potentials were recorded. During normal perfusion VL and VT were (cm/sec) 50.08 + 2.13, (SE) and 21.08 0.97. After 3 to 5 min of global ischemia, VL and VT decreased to approximately 30 and 13 cm/sec. Before the occurrence of total inexcitability propagation became time dependent (1) 2: 1 block developed and (2) centrifugal spread from the stimulus site was partially blocked at short intervals and was normal at long intervals. This suggested that slowed conduction was dependent on spatial nonuniformities of recovery from excitability. Slowing of conduction during ischemia was not explained by accumulation of [K+], alone, because VL and VT at a given [K+], were lower during ischemia than during perfusion with elevated K'. In hearts perfused at 20 mM [K+]. "'slow responses" were produced by addition of epinephrine (2.5 x 10-5M). Resting membrane potentials of slow responses were significantly lower than of depressed action potentials during ischemia. The values vL and vT of slow responses (10 and 5 cm/sec) were much lower than the lowest values during ischemia (20 and 10 cm/sec). This indicates that slow conduction in ischemia is associated with depressed action potentials initiated by a partially inactivated rapid Na+ inward current. The time dependence of nonuniform propagation and the relatively high conduction velocities explain two major characteristics of reentrant tachycardias in acute ischemia: (l) the large diameters ofreentrant circuits and (2) the beat-to-beat changes in localization of conduction block.